CPG Management of Atrial Fibrillation

MOH/P/PAK/259.
12(GU)
STATEMENT OF INTENT
This guideline is meant to be a guide for clinical practice, based on the best
available evidence at the time of development. Adherence to this guideline may
not necessarily guarantee the best outcome in every case. Every health care
provider is responsible for the management of his/her unique patient based on
the clinical picture presented by the patient and the management options
available locally.
This guideline was issued in 2011 and will be reviewed in 2016 or sooner if
new evidence becomes available
CPG Secretariat
c/o Health Technology Assessment Unit
Medical Development Division
Ministry of Health Malaysia
4th floor, Block E1, Parcel E
62590, Putrajaya.
Electronic version available on the following website:

http://www.malaysianheart.org
http:// www.moh.gov.my
http://www.acadmed.org.my
ii
FOREWORD BY PRESIDENT OF NATIONAL HEART ASSOCIATION

OF MALAYSIA (NHAM)
THE PUBLICATION of the Clinical Practice Guidelines for Atrial Fibrillation
marked a milestone in the evolution of clinical practice guidelines and the delivery
of care in cardiology. Specifically, these guidelines assist physicians in clinical
decision making by describing a range of generally acceptable approaches
for the diagnosis, management, and prevention of AF. Clinical Issues eg: AF
assessment, best treatment strategy for acute AF & reduce risk of adverse
outcomes from AF, best long term treatment strategy, management of AF in
specific special groups have been addressed in the CPG.
In a broader sense, these guidelines emphasized that AF is a worldwide public
health problem with increasing incidence and prevalence, high cost, and poor
outcomes. Importantly, this AF CPG has provided the framework for a public
health approach to improve the quality of care and outcomes of all individuals with
AF. This is a major paradigm shift from the focus on AF treatment and care that
has dominated the practice to IMPORTANT STRATEGIES eg: risk stratification,
appropriate antithrombotic therapy, safety consideration of antiarrhythmic agents
emphasized in rhythm strategy.
This latest version has undergone extensive revision in response to comments
during the public review. While considerable effort has gone into their preparation
over the past 2 years, and every attention has been paid to their detail and scientific
rigor, no set of guidelines, no matter how well developed, achieves its purpose
unless it is implemented and translated into clinical practice. Implementation is an
integral component of the process and accounts for the success of the guidelines.
The Work Group is now developing implementation tools essential to the success
of this AFCPG.
In a voluntary and multidisciplinary undertaking of this magnitude, many individuals
make contributions to the final product now in your hands. It is impossible to
acknowledge them individually here, but to each and every one of them we extend
our sincerest appreciation, especially to the members of the Writing Panel, an
effort subsequently reinforced by the review of these final guidelines by the
external reviewers. Thank you one and all for Making Lives Better for patients with
AF throughout Malaysia. A special debt of gratitude is due to the members of the
Work Group, their chair, Dr Ahmad Nizar. It is their commitment and dedication
that has made it all possible.
Professor Dr. Sim Kui Hian FNHAM

NHAM President
iii
ABOUT THE GUIDELINE

GUIDELINE DEVELOPMENT PROCESS
This is the first Clinical Practice Guideline (CPG) for Atrial Fibrillation (AF). A
committee was appointed by the National Heart Association of Malaysia (NHAM),
Ministry of Health (MOH) and the Academy of Medicine Malaysia (AMM) to draw up
this CPG. It comprises of sixteen members including cardiologists, a neurologist,
a haematologist, a cardiac surgeon, an obstetrician, a gynaecologist, general
physicians, an intensivist, a family medicine specialist and an emergency medicine
specialist from the government, private sector and the public universities.
Objectives
This CPG is intended to assist health care providers in clinical decision making
by describing a range of generally acceptable approaches for the diagnosis,
management, and prevention of AF.
Rigour of Development
Evidence was obtained by systematic review of current medical literature on Atrial
Fibrillation using the usual search engines Guidelines International Network
(G-I-N), Pubmed/Medline, Cochrane Database of Systemic Reviews (CDSR),
Database of Abstracts of Reviews of Effectiveness (DARE), Journal full text via
OVID search engine, International Health Technology Assessment websites (refer
to Appendix A for Search Terms). In addition, the reference lists of all retrieved
articles were searched to identify relevant studies. Search was limited to literature
published in English. All searches were officially conducted between 15 January
2010 and 10 December 2011. We suggest that future CPG updates will consider
evidence published after this cut-off date. The details of the search strategy can
be obtained upon request from the CPG secretariat.
Reference was also made to other guidelines on Atrial Fibrillation, Guidelines
for the Management of Atrial Fibrillation published by The Task Force for the
Management of Atrial Fibrillation of the European Society of Cardiology (ESC)
2010, The National Institute for Health and Clinical Excellence Atrial Fibrillation
Guideline 2006, Evidence-based Best Practice Guideline of New Zealand on
Atrial Fibrillation 2005 and the ACC/AHA/ESC Guidelines for the Management
of Patients With Atrial Fibrillation 2006 were also studied. These CPGs were
evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE)
prior being used as references.
Forty-three clinical questions were developed and divided into eight major sections
and members of the development panel were assigned individual questions within
these subtopics (refer to Appendix B for Clinical Questions). The group members
met a total 18 times throughout the development of the guideline. All retrieved
literature were appraised by at least two members and subsequently presented
for discussion during development group meetings.
iv
All statements and recommendations formulated were agreed collectively by

members of the Development Panel. Where the evidence was insufficient the
recommendations were derived by consensus of the Panel. These CPG are
based largely on the findings of systematic reviews, meta-analyses and clinical
trials, with local practices taken into consideration.
On completion, the draft guidelines was sent for review by external reviewers. It
was posted on the Ministry of Health of Malaysia official website for comment and
feedback from any interested parties. These guidelines had also been presented
to the Technical Advisory Committee for CPG, and the HTA and CPG Council,
Ministry of Health of Malaysia for review and approval.
The level of recommendation and the grading of evidence used in this guideline
were adapted from the American Heart Association and the European Society of
Cardiology (AHA/ESC) and outlined on page xi. In the text, this is written in black
and boxed on the left hand margin.
Sources of Funding
Sanofi Aventis (M) Sdn. Bhd. supported the development of the CPG on
Management of Atrial Fibrillation financially. However, the views of the funding
body have not influenced the content of the guideline.
Disclosure statement
The development panel members had completed disclosure forms. None held
shares in pharmaceutical firms or acted as consultants to such firms. (Details are
available upon request from the CPG Secretariat)
Clinical Issues Addressed
1. How do you assess a patient suspected of having atrial fibrillation?
2. What is the best strategy to treat patients with atrial fibrillation in the acute
setting?
3. What is the best strategy to reduce the risk of adverse outcomes from atrial
fibrillation?
4. What is the best long-term management strategy?
5. How to manage atrial fibrillation in specific special groups?
Target Group
This CPG is directed at all healthcare providers treating patients with AF
allied professionals, family and general physicians, medical officers, emergency
physicians, intensivists and cardiologists.
Target Population
It is developed to assist clinical decision making for all adults and pregnant
women with AF.
Period of Validity of the Guidelines

This guideline needs to be revised at least every 5 years to keep abreast with
recent developments and knowledge.
Implementation of the Guidelines
To ensure successful implementation of this CPG we suggest:
1. Constant checks and feedback on whether the guideline is relevant.
2. Identify implementation leaders

Identification of multiple leaders to share the implementation work and ensure

seamless care. These leaders are likely to be prominent figures who will
champion the guideline and inspire others.
3. Identify an implementation group

Support from medical associations such as the Private Medical Practitioners

Society (PMPS), Society of Pacing and Electrophysiology (SOPACE)
and Malaysian Medical Association (MMA) will help dissemination of the
guidelines.
4. Carrying out a baseline assessment

This involves comparing current practice with the recommendations. The audit
criteria will help this baseline assessment.
5. Developing an action plan

The baseline assessment will have identified which recommendations are

not currently being carried out. These recommendations could be put into an
action plan.
6. Key areas for implementation

We have identified several goals for implementation based on the key priorities
for implementation identified in the guideline
vi
GUIDELINE WORKING GROUP

Chairperson
Dr Ahmad Nizar b Jamaluddin
Consultant Cardiologist & Electrophysiologist
Sime Darby Medical Centre
Selangor
Dr Anita bt Alias
Intensivist
Hospital Melaka
Melaka
Datuk Dr Hj Azhari b Rosman,
Consultant Cardiologist & Electrophysiologist
National Heart Institute
Kuala Lumpur
Dato Dr Chang Kian Meng
Consultant Heamatologist & Head of Department
Department of Haematology
Hospital Ampang
Kuala Lumpur
Dr Ernest Ng Wee Oon
Consultant Cardiologist and Electrophysiologist
Pantai Hospital KL
Kuala Lumpur
Dr Hashim b Tahir
Consultant Obstetrician & Gynaecologist
Universiti Technologi MARA
Selangor
Associate Professor Dr Imran b Zainal Abidin
Associate Professor of Medicine & Consultant Cardiologist
University Malaya Medical Centre
Kuala Lumpur
Dr Jeswant Dillon
Consultant Cardiothoracic Surgeon
National Heart Institute
Kuala Lumpur
vii
Professor Dato Dr Khalid b Haji Yusoff,

Professor of Medicine and Senior Consultant Cardiologist
Universiti Teknologi MARA
Selangor
Dr Lai Voon Ming
Consultant Cardiologist and Electrophysiologist
Sri Kota Medical Centre
Selangor
Dr Ngau Yen Yew
Consultant Physician
Hospital Kuala Lumpur
Kuala Lumpur
Dato Dr Omar b Ismail,
Consultant Cardiologist & Head of Department
Department of Cardiology
Hospital Pulau Pinang
Prof. Madya Dr Oteh b Maskon
Consultant Cardiologist & Head of Department
Hospital Universiti Kebangsaan Malaysia
Kuala Lumpur
Datuk Dr Raihanah bt Abdul Khalid
Consultant Neurologist
Pantai Hospital KL
Kuala Lumpur
Dr Ridzuan b Dato Mohd Isa
Emergency Medicine Specialist & Head of Department
Department of Accident & Emergency
Hospital Ampang
Kuala Lumpur
Dr V Paranthaman
Family Medicine Specialist & Head of Department
Klinik Kesihatan Jelapang
Perak
viii
EXTERNAL REVIEWERS
1)

Dato Dr Ravindran Jegasothy

Senior Consultant & Head of Department
Obstetrics & Gynaecology
Hospital Kuala Lumpur
2)

Datuk Dr Razali b Omar

Deputy Head, Consultant Cardiologist & Electrophysiologist
Director of Clinical Electrophysiology & Pacemaker Service
3)

Professor Dr Sim Kui Hian

Visiting Senior Consultant Cardiologist
Sarawak General Hospital Heart Centre
Adjunct Professor
Faculty of Medicine & Health Sciences
University Malaysia Sarawak (UNIMAS)
4)

Dato Dr. Sree Raman

Senior Consultant Physician
Hospital Tuanku Jaafar
Seremban
5)

Dr Tai Li Ling
Consultant Intensivist
Department of Anaesthesia and Intensive Care
Hospital Kuala Lumpur.
ix
SUMMARY
KEY MESSAGES
1
An electrocardiogram (ECG) should be performed in all patients, whether

symptomatic or not, in whom AF is suspected because an irregular pulse
has been detected.
The stroke risk stratification algorithms, CHADS2 and CHA2DS2VASc,

should be used in patients with AF to assess their risk of stroke and
thrombo-embolism, while the HAS-BLED score should be used to assess
their risk of bleeding.
Antithrombotic therapy should be based upon the absolute risks of stroke/

thrombo-embolism and bleeding, and the relative risk and benet for a
given patient.
When choosing either an initial rate-control or rhythm-control strategy, the

indications for each option should not be regarded as mutually exclusive
and the potential advantages and disadvantages of each strategy should be
explained to patients before agreeing which to adopt. Any comorbidities that
might indicate one approach rather than the other should be taken into
account . Irrespective of whether a rate-control or a rhythm-control strategy
is adopted in patients with persistent or paroxysmal AF, appropriate
antithrombotic therapy should be used.
When choosing an antiarrhythmic agent for rhythm control strategy, safety

rather than efficacy considerations should primarily guide the choice of
antiarrhythmic agent.
In patients with permanent AF, who need treatment for rate control, betablockers or rate-limiting calcium antagonists should be the preferred initial
monotherapy in all patients while digoxin should only be considered as
monotherapy in predominantly sedentary patients.
The management cascade for patients with AF. ACEI = angiotensin-converting enzyme inhibitor; AF = atrial
fibrillation; ARB = angiotensin receptor blocker; PUFA = polyunsaturated fatty acid; TE = thrombo-embolism.
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart
Journal 2010; doi:10.1093/eurheartj/ehq278)
xi
<<ATRIAL
<<ATRIAL
FIBRILLATION
FIBRILLATION
MANAGEMENT
MANAGEMENT
CASCADE>>
CASCADE>>
Grading
Grading
System
System
The
The
format
format
used
used
forfor
Classification
Classification
of of
Recommendations
Recommendations
andand
Level
Level
of of
Evidence
Evidence
was
was
adapted
adapted
from
from
thethe
American
American
Heart
Heart
Association
Association
andand
thethe
European
European
Society
Society
of of
Cardiology.
Cardiology.
GRADES
GRADES
OFOF
RECOMMENDATIONS
RECOMMENDATIONS
AND
AND
LEVELS
LEVELS
OFOF
EVIDENCE
EVIDENCE
GRADES
OFOF
RECOMMENDATION
GRADES
RECOMMENDATION
I I
II II
Conditions
which
there
is evidence
and/or
general
agreement
Conditions
forfor
which
there
is evidence
and/or
general
agreement
a given
procedure/therapy
is beneficial,
useful
and/or
thatthat
a given
procedure/therapy
is beneficial,
useful
and/or
effective.
effective.
Conditions
forfor
which
there
is conflicting
evidence
and/or
Conditions
which
there
is conflicting
evidence
and/or
divergence
of opinion
about
thethe
usefulness/efficacy
of aof a
divergence
of opinion
about
usefulness/efficacy
procedure/therapy.
procedure/therapy.
II-aII-a
Weight
of evidence/opinion
is in
of its
usefulness/efficacy.
Weight
of evidence/opinion
is favor
in favor
of its
usefulness/efficacy.
II-bII-b
Usefulness/efficacy
is less
well
established
by by
evidence/opinion
Usefulness/efficacy
is less
well
established
evidence/opinion
III III
Conditions
forfor
which
there
is evidence
and/or
general
agreement
Conditions
which
there
is evidence
and/or
general
agreement
thatthat
a procedure/therapy
is not
useful/effective
andand
in some
a procedure/therapy
is not
useful/effective
in some
cases
may
be be
harmful.
cases
may
harmful.
LEVELS
OFOF
EVIDENCE
LEVELS
EVIDENCE
A A
B B
C C
Data
derived
from
multiple
randomised
clinical
trials
or meta
Data
derived
from
multiple
randomised
clinical
trials
or meta
analyses
analyses
Data
derived
from
a single
randomised
clinical
trialtrial
or large
nonnon
Data
derived
from
a single
randomised
clinical
or large
randomised
studies
randomised
studies
Only
consensus
of opinions
of experts,
case
studies
or standard
Only
consensus
of opinions
of experts,
case
studies
or standard
of care
of care
Adapted from the American Heart Association/American College of Cardiology (AHA/

ACC) and the European Society of Cardiology (ESC)
xii
TABLE OF CONTENTS
Statement of Intent
Foreword
About the Guideline
Guideline Development Process
Guideline Working Group
External Reviewer
Summary
Key Messages
Atrial Fibrillation Management Cascade
Grading System
Table of Content
I. Introduction
1.1 Definition
1.2 Types of Atrial Fibrillation
1.3 AF Natural Time Course
1.4 Epidemiology and Prognosis
2.
Pathophysiology
2.1. Clinical Aspects
2.1.1. Causes and Associated Conditions
3.
Initial Management
3.1. Clinical History and Physical Examination and Investigations
3.1.1. Detection
3.1.1.1. Electrocardiogram
3.1 Diagnostic Evaluation
3.2 Echocardiogram
3.3 Clinical Follow-up
4 Management Principles
4.1 General Principles
4.2 Thromboembolic Prophylaxis
4.3 Heart Rate vs Rhythm Control
5 Management Acute-onset AF
5.1 Acute AF In Hemodynamically Unstable Patients
5.1.1 Acute Rate Control
5.1.2 Pharmacological Cardioversion
5.1.2.1
Pill-in-the-pocket Approach
5.1.3 Direct Current Cardioversion
5.1.3.1
Procedure
5.1.3.2
Complications
5.1.3.3
Cardioversion In Patients With Implanted
Pacemakers And Defibrillators
5.1.3.4
Recurrence After Cardioversion
5.1.4 Antithrombotic Therapy For Acute-onset AF
6 Management - Prevention of Thromboembolism
xiii
6.1 Risk Stratification For Stroke

6.2 Strategies for Thromboembolic Prophylaxis
6.3 Antithrombotic Therapy
6.3.1 Anticoagulation With Vitamin K Antagonists
6.3.2 Optimal International Normalized Ratio
6.3.2.1
Point-of-care testing and self-monitoring of
anticoagulation
6.3.3 Anticoagulation With Direct Thrombin Inhibitors
6.3.4 Investigational Agents
6.3.5 Antiplatelet Agent Aspirin
6.3.6 Aspirin And Clopidogrel Combination
6.4 Anticoagulation In Special Circumstances
6.4.1 Peri-operative Anticoagulation
6.4.2 Acute Stroke
6.4.3 Anticoagulant and Antiplatelet Therapy Use in Patients With
Atrial Fibrillation Undergoing Percutaneous Coronary
Intervention
6.4.4 Non-ST Elevation Myocardial Infarction
6.4.5 Cardioversion
6.5 Non-pharmacological Methods To Prevent Strokes
6.6 Risk of Long-term Anticoagulation
6.6.1 Assessment Of Risk Of Bleeding
6.6.2 Risk Score For Bleeding
7 Management Long-term Rate Control
7.1 Pharmacological Rate Control
7.1.1 Combination Therapy
7.2 Non-Pharmacological Rate Control
7.2.1 AV Nodal Ablation And Pacing
8 Management Long-term Rhythm Control
8.1 Efficacy Of Antiarrhythmic Drugs In Preventing Recurrent AF
8.2 Choice Of Antiarrhythmic drugs
8.2.1 Patients With Lone AF
8.2.2 Patients With Underlying Heart Disease
8.2.2.1
Patients With Left Ventricular Hypertrophy
8.2.2.2
Patients With Coronary Artery Disease
8.2.2.3
Patients With Heart Failure
8.3 Non-Pharmacological Therapy
8.3.1 Left Atrial Catheter Ablation
8.3.2 Surgical Ablation
8.3.3 Suppression of AF Through Pacing
8.4 Upstream Therapy
8.4.1 Angiotensin-converting Enzyme Inhibitors and Angiotensin
Receptor Blockers
8.4.2 Statins
8.4.3 Polyunsaturated Fatty Acids and Aldosterone Antagonist
9 Management Special Populations
xiv
9.1 Post-Operative AF
9.1.1 Prevention Of Post-operative AF
9.1.2 Treatment of Post-operative AF
9.2 Acute Coronary Syndrome
9.3 Wolff-Parkinson-White (WPW) Pre-excitation Syndromes
9.3.1 Sudden Death And Risk Stratification
9.4 Hyperthyroidism
9.5 Pregnancy
9.6 Hypertrophic Cardiomyopathy
9.7 Pulmonary Diseases
9.8 Heart Failure
9.9 Athletes
9.10 Valvular Heart Disease
10 Referrals
11 Audit and Evaluation
Appendixes
Glossary
References
xv
1 INTRODUCTION
1.1 DEFINITION
Atrial fibrillation (AF) is an atrial tachyarrhythmia characterized by uncoordinated
atrial activation with consequent deterioration of atrial mechanical function. The
surface ECG is characterized by absolutely irregular RR intervals and the
absence of any distinct P waves. The P waves are replaced by fibrillary (F)
waves.
Atrial Flutter (AFl) in the typical form is characterized by a saw-tooth pattern of
regular atrial activation called flutter (F) waves on the ECG. AFl commonly
occurs with 2:1 AV block, resulting in a regular or irregular ventricular rate of 120
to 160 beats per minute (most characteristically about 150 beats per minute).
1.2 TYPES OF ATRIAL FIBRILLATION
Clinically, five types of AF are recognized based on the presentation and the
duration of the episode. These categories are set out below. (See Table 1 and
Figure 2)
<<Table 1 >>
Table 1. Classification of AF subtypes
The term
lone AF applies to young
individuals
Terminology
Clinical
Features (under 60 years of age)
Patternwithout
clinical
or(first
echocardiographic
Initial event
Symptomaticevidence of cardiopulmonary disease,
May or mayincluding
not recur
detected episode) These Asymptomatic
hypertension.
patients have a favourable prognosis with respect to
Onset unknown
thromboembolism
andSpontaneous
mortality. termination <7 days and most often < Recurrent
Paroxysmal
48 hours
Persistent
Not self terminating
Recurrent
Silent
AF being asymptomatic
is detected by an opportunistic
ECG or may
Lasting >7 days or requiring cardioversion for
present as an AF-related
complication such as ischemic stroke.
termination
Long standing persistent
AF that has lasted for
Recurrent
Permanent
Not terminated
Terminated but relapsed
No cardioversion attempt
Established
1 yearfor
when
it is decided
to adopt a rhythm
control
This classication is useful
clinical
management
of AF
patients (Figure 1),
strategysymptoms are also considered.
especially when AF-related
<<Figure 1>>
1.3 AF NATURAL TIME COURSE

Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010
AF is a naturally
progressive
disease
for a small proportion of patients (2Version)
(European
heart Journal
2010;except
doi:10.1093/eurheartj/ehq278)
3%), who are free of AF-promoting conditions (see section 2.1.1, page 5), may
remain in paroxysmal AF over several decades.1 AF progresses from short rare
episodes, to longer and more frequent attacks (See Figure 2). With time, often
years, many patients will develop sustained forms of AF. Paroxysm of AF
episodes also occurs in cluster and AF burden can vary markedly over months
or years.2

duration of the episode. These categories are set out below. (See Table 1 and
Figure 2)
<<Table 1 >>
The term lone AF applies to young individuals (under 60 years of age) without
clinical or echocardiographic evidence of cardiopulmonary disease, including
hypertension. These patients have a favourable prognosis with respect to
thromboembolism and mortality.
Silent AF being asymptomatic is detected by an opportunistic ECG or may
as an AF-related complication such as ischemic stroke.
1present
INTRODUCTION
1 INTRODUCTION
ThisDEFINITION
classication is useful for clinical management of AF patients (Figure 1),
1.1
1.1
DEFINITION
especially
when AF-related symptoms are also considered.
Atrial fibrillation (AF) is an atrial tachyarrhythmia characterized by uncoordinated
Atrial
fibrillation
is an atrial tachyarrhythmia
by uncoordinated
<<Figure
1>> (AF)
atrial
activation
with consequent
deterioration of characterized
atrial mechanical
function. The
atrial
activation
consequentby
deterioration
atrial mechanical
function.
surface
ECG iswith
characterized
absolutelyofirregular
RR intervals
and The
the
surface
ECG
is distinct
characterized
by The
absolutely
irregular
RR intervals
and the
1.3 AF NATURAL
TIME COURSE
absence
of any
P waves.
P waves
are replaced
by fibrillary
(F)
absence
waves. of any distinct P waves. The P waves are replaced by fibrillary (F)
waves.
AF is a naturally progressive disease except for a small proportion of patients (23%), who
are(AFl)
free in
of the
AF-promoting
(see section
2.1.1, page
5), may
Atrial
Flutter
typical formconditions
is characterized
by a saw-tooth
pattern
of
Atrial
(AFl)
in the
typical
form is(F)
characterized
by aECG.
saw-tooth
pattern
of
from commonly
short rare
remainFlutter
in
paroxysmal
AFcalled
over several
decades.
regular
atrial
activation
flutter
waves1 AF
on progresses
the
AFl
regular
atrial
activation
called
flutter
(F)
waves
on
the
ECG.
AFl
commonly
episodes,
longer
and more
frequent
attacksor(See
Figure
2). With rate
time,ofoften
occurs
withto2:1
AV block,
resulting
in a regular
irregular
ventricular
120
occurs
with
2:1
AV
block,
resulting
in sustained
a regular or
irregular
ventricular
rate of
years,
many
patients
will
develop
forms
of beats
AF.
Paroxysm
of 120
AF
to
160 beats
per
minute
(most
characteristically
about
150
per minute).
to
160 beats
minute
150 beats
per minute).
episodes
alsoper
occurs
in (most
clustercharacteristically
and AF burdenabout
can vary
markedly
over months
2
or years.
1.2
TYPES OF ATRIAL FIBRILLATION
Clinically,
of AF
are recognized
presentation
and1the
duration offive
thetypes
episode.
These
categories based
are seton
outthe
below.
(See Table
and
duration
Figure 2)of the episode. These categories are set out below. (See Table 1 and
Figure 2)
<<Table 1 >>
<<Table 1 >>
The term lone AF applies to young individuals (under 60 years of age) without
without
The term
AF applies to young
individuals
(under 60 years
of age)including
clinical
orlone
echocardiographic
evidence
of cardiopulmonary
disease,
clinical
or echocardiographic
cardiopulmonary
including
hypertension.
These patients evidence
have a of
favourable
prognosisdisease,
with respect
to
hypertension.
These
thromboembolism
and patients
mortality. have a favourable prognosis with respect to
thromboembolism and mortality.
Silent AF being asymptomatic is detected by an opportunistic ECG or may
Silent
being
asymptomatic
is detected
an opportunistic
ECG or may
presentAF
as an
AF-related
complication
such asby
ischemic
stroke.
present as an AF-related complication such as ischemic stroke.
Figure
Different types is
of AF.
AF =for
atrial
fibrillation;
CV = cardioversion.
arrhythmia
tends to
This 1:
classication
useful
clinical
management
of AFThe
patients
(Figure
1),progress
from
paroxysmal
(self-terminating,
usually
h) to persistent
[non-self-terminating
This
classication
is useful for
clinical,48management
of AF
patients (Figureor1),requiring
especially
when
AF-related
symptoms
are longer
also considered.
cardioversion
(CV)], long-standing
persistent
(lasting
than 1 year) and eventually to permanent
especially when AF-related symptoms are also considered.
(accepted) AF. First-onset AF may be the first of recurrent attacks or already be deemed permanent.
<<Figure
Adapted
from 1>>
the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart
<<Figure
1>>
AF is a naturally progressive disease except for a small proportion of patients (2AF

a naturally
progressive
diseaseconditions
except for(see
a small
proportion
patients
(23%),is who
are free
of AF-promoting
section
2.1.1, of
page
5), may
1
3%),
who
are free of AF-promoting
conditions
section
2.1.1,from
pageshort
5), may
AF
progresses
rare
remain
in paroxysmal
AF over several
decades.(see
1
AF progresses
fromtime,
shortoften
rare
remain
in paroxysmal
AFmore
over frequent
several decades.
episodes,
to longer and
attacks (See
Figure 2). With
episodes,
to longer
andwill
more
frequent
attacks (See
With time,ofoften
years, many
patients
develop
sustained
formsFigure
of AF.2).Paroxysm
AF
years, many
develop
sustained
of AF.
Paroxysm
of AF
episodes
also patients
occurs inwill
cluster
and AF
burdenforms
can vary
markedly
over months
2
episodes
or
years. also occurs in cluster and AF burden can vary markedly over months
or years.2
Asymptomatic AF is common even in symptomatic patients, irrespective of
whether the initial presentation was persistent or paroxysmal. This has important
implications for strategies aimed at preventing AF-related complications.
<<Figure 2>>
Figure22: :Natural
Naturaltime
timecourse
courseof
of AF.
AF. AF
AF == atrial
atrial fibrillation.
fibrillation. The dark blue boxes show aa typical
Figure
typical sequence
sequence of
of
periodsininAF
AF against
against aa background
background of
of sinus
sinus rhythm,
rhythm, and
and illustrate the progression of
periods
of AF
AF from
from silent
silent and
and
undiagnosedtotoparoxysmal
paroxysmal and
and chronic
chronic forms,
forms, at
at times
times symptomatic. The upper bars
undiagnosed
bars indicate
indicate therapeutic
therapeutic
measures that
that could
could be
be pursued.
pursued. Light
Light blue
blue boxes
boxes indicate
indicate therapies that have proven
measures
proven effects
effects on
on hard
hard
Asymptomatic
AF
is
common
even
in Red
symptomatic
irrespective
of
outcomesininAF,
AF,such
such
asstroke
stroke
or acute
acute heart
heart
failure.
Red
therapies that
are
outcomes
as
or
failure.
boxes indicatepatients,
that
are currently
currently used
used
forsymptom
symptom
relief,
but may
may
in the
the future
futurewas
contribute
to reduction
reduction
Rate
for
relief,
but
in
contribute
to
of AF-related complications.
complications.
Rate control
control
whether
the
initial
presentation
persistent
or paroxysmal.
This has important
(greybox)
box)isisvaluable
valuable
forsymptom
symptomaimed
relief and
and
may
improve cardiovascular
outcomes.
(grey
for
relief
improve
implications
for strategies
atmay
preventing
AF-related
complications.
<<Figure
Journal 2010;2>>
1.4 EPIDEMIOLOGY AND PROGNOSIS

AF is the commonest sustained cardiac arrhythmia. Information on AF in
Malaysia is scarce. Hospital practice data may give a biased view of the clinical
epidemiology of AF, since only one-third of patients with AF may actually have
been admitted to hospital.
Data from predominantly western populations suggest the estimated prevalence
of AF is 0.4% to 1% in the general population. The prevalence of AF doubles with
each decade of age, from 0.5% at age 50-59 years to almost 9% at age 80-89
years.3-4
The mortality rate of patients with AF is about double that of patients in sinus
rhythm.2,5
AF is associated with a prothrombotic state, intra-atrial stasis, structural heart
disease or blood vessel abnormalities and abnormal platelets haemostasis,
leading to a predisposition to thrombus formation. This prothrombotic state leads
to stroke and thromboembolism in AF (See Table 1, Page 1). Only antithrombotic
therapy has been shown to reduce AF-related deaths.6
<<Table 2 >>
3
Stroke in AF is often severe and results
in long-term disability or death.
Approximately 20% of stroke is due to AF and undiagnosed silent AF is a likely
Table 2: Clinical events (outcomes) affected by AF
Relative change in AF
patients
Outcome parameter
Asymptomatic AF is common even in symptomatic patients, irrespective of

1. Death
Death
doubled.
whether the initial presentation was persistent
or rate
paroxysmal.
This has important
implications for strategies aimed at preventing AF-related complications.
Stroke risk increased; AF is

associated with more severe
stroke.
2. Stroke (includes
haemorrhagic
stroke and
<<Figure
2>>
cerebral bleeds)
Hospitalizations are frequent in
1.4
AND PROGNOSIS AF patients and may contribute
3. EPIDEMIOLOGY
Hospitalizations
to reduced quality of life.
AF is the commonest sustained cardiac arrhythmia. Information on AF in

Malaysia is scarce. Hospital practice data may give a biased view of the clinical
variation,
effect
epidemiology of AF, since only one-thirdWide
of patients
with AFfrom
may no
actually
have
been admitted to hospital.
to major reduction.
4. Quality of life and exercise
AF can cause marked distress
Data capacity
from predominantly western populations suggest the estimated prevalence
through palpitations and other
of AF is 0.4% to 1% in the general population. The prevalence of AF doubles with
AF-related
each decade of age, from 0.5% at age 50-59
years tosymptoms.
almost 9% at age 80-89
years.3-4
Wide variation, from no change
5. Left ventricular function
The mortality rate of patients with AF isto

about
double that of patients with
in sinus
tachycardiomyopathy
rhythm.2,5
acute heart failure.
AF is associated with a prothrombotic state, intra-atrial stasis, structural heart

disease
or fibrillation.
blood vessel abnormalities and abnormal platelets haemostasis,
AF = atrial
leading
to a are
predisposition
to thrombus order
formation.
This prothrombotic
state leads
Outcomes
listed in hierarchical
modified
from a suggestion
put
Only
antithrombotic
to
stroke in
and
thromboembolism
in AF (See 2Table
1, Page 1). of
forward
a recent
consensus document.
The prevention
these
outcomes
therapy has been shown to reduce AF-related deaths.6
is the main therapeutic goal in AF patients.
<<Table 2 >>
Stroke in AF is often severe and results in long-term disability or death.
Approximately 20% of stroke is due to AF and undiagnosed silent AF is a likely
cause of some cryptogenic strokes.2,7 Paroxysmal AF carries the same stroke
risk as permanent or persistent AF.8
AF also account for one-third of all admissions for cardiac arrhythmias. Acute
Coronary Syndrome (ACS), aggravation of heart failure, thrombo-embolic
complications, and acute arrhythmia management are the main causes.
Quality of life and exercise capacity are degraded in patients with AF.9 This may
be related to impaired left ventricular (LV) function that accompanies the
irregular, fast ventricular rate, loss of atrial contractile function and increased
end-diastolic LV lling pressure.
2. PATHOPHYSIOLOGY
Understanding the pathophysiology of atrial brillation (AF) requires integration
of
information
from
clinical,
histological,
electrophysiological
and
echocardiographic sources. There is no single cause or mechanism that results
in AF, and it may present in a multitude of ways.
2.1 CLINICAL ASPECTS
There are many risk factors for developing AF. In the Framingham study the
development of AF was associated with increasing age, diabetes, hypertension
and valve disease. It is also commonly associated with, and complicated by HF
and strokes.
2.1.1 CAUSES AND ASSOCIATED CONDITIONS
AF is often associated with co-existing medical conditions. The underlying
conditions and factors predisposing patients to AF are listed in Table 3.
<<Table 3 >>
Table 3: Common cardiac and non-cardiac risk factors of AF.
Some of the conditions predisposing to AF may be reversible such as acute

Elevated Atrial Pressure
infections,
alcohol excess, surgery, pericarditis, myocarditis, pulmonary
Systemic Hypertension
pathology
and thyrotoxicosis. Therefore, long-term therapy of AF may not be
Pulmonary Hypertension
Myocardial disease
with systolic
and/orhave
diastolicbeen
dysfunction)
indicated
once (cardiomyopathy
the reversible
causes
addressed. When AF is
Mitral or tricuspid valve disease
associated
withvalve
other
supraventricular arrhythmias, treatment of the primary
Aortic or pulmonary
disease
arrhythmia
reduces or eliminates the recurrence of AF.
Intracardiac tumours
Sleep apnoea
Atrial ischemia
Coronary artery disease
Approximately
30 40%
of cases of paroxysmal AF
Inflammatory or infiltrative
atrial disease
Myocarditis
AF
occur orinpericarditis
young patients without demonstrable
Amyloidosis
cases
are often
referred to as lone AF.
Age-induced
atrial fibrosis
Primary or metastatic cancer in/or adjacent to the atrial wall
Drugs
Alcohol
Caffeine
Endocrine disorders
Hyperthyroidism
Phaeochromocytoma
Changes in autonomic tone
Increased sympathetic tone
Increased parasympathetic tone
Postoperative
Cardiothoracic surgery
Oesophageal surgery
Neurogenic
Subarchnoid haemorrhage
Haemorrhagic stroke
Ischemic stroke
Idiopathic
Lone AF
Familial AF
Other
Congenital heart disease
Chronic renal disease
Obesity
and 20 25% of persistent

underlying disease. These
2.1.1 CAUSES AND ASSOCIATED CONDITIONS

AF is often associated with co-existing medical conditions. The underlying
conditions and factors predisposing patients to AF are listed in Table 3.
<<Table 3 >>
Some of the conditions predisposing to AF may be reversible such as acute
infections, alcohol excess, surgery, pericarditis, myocarditis, pulmonary
pathology and thyrotoxicosis. Therefore, long-term therapy of AF may not be
indicated once the reversible causes have been addressed. When AF is
associated with other supraventricular arrhythmias, treatment of the primary
arrhythmia reduces or eliminates the recurrence of AF.
Approximately 30 40% of cases of paroxysmal AF and 20 25% of persistent
AF occur in young patients without demonstrable underlying disease. These
cases are often referred to as lone AF.
3 INITIAL MANAGEMENT
3.1 CLINICAL HISTORY, PHYSICAL EXAMINATION AND INVESTIGATIONS
The acute management of AF patients should concentrate on
Relief of symptoms
Assessment of AF-associated risk
Determination of the European Heart Rhythm Association (EHRA) score
(Table 5, page 7)
Estimation of stroke risk (see Section 6.1, page 26)
Search for conditions that predispose to AF (see Section 2.1.1, page 5) and
Search for complications of the arrhythmia (see Section 1.4, page 3)
With the above in mind, a thorough medical history should be obtained from the
patient with suspected or known AF (see Table 4).
Table 4:
4: Relevant
Relevant questions
to be
be put
put to
to a
a patient
patient with
with suspected
suspected or
or known
known AF
AF
Table
<<Table
4>> questions to
Does the heart rhythm during the episode feel regular or irregular?
The
EHRA any
symptom
score (seefactor
Tablesuch
5) provides
a simpleemotion,
clinical tool
Is there
precipitating
as exercise,
or for
assessing symptoms during AF. The score only considers symptoms that are
alcohol intake?
attributable to AF and reverse or reduce upon restoration of sinus rhythm or with
effective rate control.
Are symptoms during the episodes moderate or severethe severity
may be5 expressed

using the EHRA score,3 which is similar to the
<<Table
>>
CCS-SAF score.41
Are the episodes frequent or infrequent, and are they long or short
3.1.1
DETECTION
lasting?
Those with undiagnosed AF can receive treatment sooner if an opportunistic

Is there a history of concomitant disease such as hypertension,
case finding is undertaken. Routine palpation of the radial pulse (not less than 20
coronaryduring
heartscreening
disease,
heart pressure
failure, will
peripheral
vascular
disease,
seconds)
of blood
be a good
opportunity
to pick up
cerebrovascular
disease, stroke, diabetes, or chronic pulmonary
undiagnosed
atrial fibrillation.
disease?
In patients presenting with any of the following:

breathlessness/dyspnoea,
Is xthere
an alcohol abuse habit?
x palpitations,
syncope/dizziness,
Is xthere
a family history of AF?
x chest discomfort or stroke/TIA,
manual
pulse palpation
performedSociety
to assess
for
theFibrillation;
presence
of== an
AF
CCS-SAF
Canadian
Cardiovascular
Severity
Atrial
EHRA
AF =
= atrial
atrial fibrillation;
fibrillation;
CCS-SAF =
=should
Canadianbe
Cardiovascular
Society
Severity in
in
Atrial
Fibrillation;
EHRA
European Heart
Heart
Rhythm
Association.
European
Rhythm
irregular
pulse
thatAssociation.
may indicate AF.
6
patient with suspected or known AF (see Table 4).
<<Table 4>>
3 INITIAL MANAGEMENT
The EHRA symptom score (see Table 5) provides a simple clinical tool for
3.1 CLINICAL HISTORY, PHYSICAL EXAMINATION AND INVESTIGATIONS
assessing symptoms during AF. The score only considers symptoms that are
The acute management of AF patients should concentrate on
effective rate control.
Relief of symptoms
Assessment of AF-associated risk
<<Table 5 >>
Determination of the European Heart Rhythm Association (EHRA) score
Table 5 : EHRA score of AF-related symptoms
(Table 5, page 7)
Estimation of stroke risk (see Section 6.1, page 26)
Search
for conditions of
that
predisposesymptoms
to AF (see Section
page 5) and
Classification
AF-related
(EHRA2.1.1,
score)
3.1.1 DETECTION
Search for complications of the arrhythmia (see Section 1.4, page 3)
Explanation
EHRAwith
class
Those
undiagnosed AF can receive treatment sooner if an opportunistic
patient
with
suspected
or known
AF (see Table 4).
No
symptoms
EHRA
I
seconds) during screening
of blood pressure will be a good opportunity to pick up
undiagnosed atrial fibrillation.
<<Table
EHRA 4>>
II
Mild symptoms; normal daily activity not affected

EHRA
III
Severe symptoms; normal daily activity affected
x breathlessness/dyspnoea,
palpitations,
Thex EHRA
symptom score (see Table 5) provides a simple clinical tool for
symptoms; normal daily activity
x syncope/dizziness,
EHRA
IVsymptomsDisabling
assessing
during AF. The score only considers symptoms that are
discontinued
x
chest
discomfort
or
stroke/TIA,
manual
palpation should be performed to assess for the presence of an
effectivepulse
rate control.
irregular pulse that may indicate AF.
AF = atrial fibrillation; EHRA = European Heart Rhythm Association.
<<Table 5 >>
3.1.1 DETECTION
Those with undiagnosed AF can receive treatment sooner if an opportunistic
seconds) during screening of blood pressure will be a good opportunity to pick up
undiagnosed atrial fibrillation.
x breathlessness/dyspnoea,
x palpitations,
x syncope/dizziness,
x chest discomfort or stroke/TIA,
manual pulse palpation should be performed to assess for the presence of an
irregular pulse that may indicate AF.
3.1.1.1 ELECTROCARDIOGRAM
The diagnosis of AF requires confirmation by ECG, sometimes in the form
of bedside telemetry, ambulatory Holter recordings and event loop
recordings. 2, 10
If AF is present at the time of recording, a standard 12-lead ECG is sufficient to
confirm the diagnosis. In paroxysmal AF, 7-days Holter ECG recording or daily
and symptom-activated event recordings may document the arrhythmia in 70% of
AF patients.2
The search for AF should be intensified;
7 including prolonged monitoring, when
patients
of bedside telemetry, ambulatory Holter recordings and event loop

recordings. 2, 10
If AF is present at the time of recording, a standard 12-lead ECG is sufficient to
confirm the diagnosis. In paroxysmal AF, 7-days Holter ECG recording or daily
and symptom-activated event recordings may document the arrhythmia in 70% of
AF patients.2
The search for AF should be intensified; including prolonged monitoring, when
patients
Are highly symptomatic (EHRA III & IV)
Present with recurrent syncope and
After a cryptogenic stroke.11, 12
In stroke survivors, a step-wise addition of ve daily short-term ECGs, one 24 h
Holter ECG, and another 7-day Holter ECG will each increase the detection rate
of AF by a similar extent.11
3.2 DIAGNOSTIC EVALUATION
The initial diagnostic work-up is driven by the initial presentation.
The time of onset of AF should be established to dene the type of AF (Figure 2).
Patients with AF and signs of acute heart failure require urgent rate control and
often cardioversion. An urgent transthoracic echocardiogram (TTE) should be
performed in haemodynamically-compromised patients to assess LV and valvular
function and right ventricular pressure. If AF duration is >48 h or there is doubt
about its duration, transesophageal echocardiogram (TOE) should be used to
rule out intracardiac thrombus prior to cardioversion.13
Patients with stroke or TIA require immediate stroke diagnosis, usually via
emergency computed tomography (CT).
Patients should be assessed for risk of stroke. Most patients with acute AF will
require anticoagulation unless they are at low risk of thromboembolic
complications (no stroke risk factors) and no cardioversion is necessary (e.g. AF
terminates within 24 48 h).
After the initial management of symptoms and complications, underlying causes
of AF should be sought. A TTE is useful to detect ventricular, valvular, and atrial
disease as well as rare congenital heart disease. Thyroid function tests, a full
blood count, a serum creatinine measurement and analysis for proteinuria,
measurement of blood pressure, and a test for diabetes mellitus are useful. A
serum test for hepatic function may be considered in selected patients. A stress
test is reasonable in patients with signs or risk factors for coronary artery
disease. Patients with persistent signs of LV dysfunction and/or signs of
myocardial ischemia are candidates for coronary angiography
Table 6 lists the clinical evaluation that may be necessary in patients with AF.
<<Table 6 >>
3.3 ECHOCARDIOGRAPHY
TTE should be performed in patients with AF:
o For whom a baseline echocardiogram is important for long-term
management.
o For whom a rhythm-control strategy that includes cardioversion
(electrical or pharmacological) is being considered.
o In whom there is a high risk or a suspicion of underlying
structural/functional heart disease
(such as heart failure or heart
8
murmur) that influences their subsequent management (for
Table 6 : Clinical Evaluation in Patients With AF

Minimum evaluation
1. Electrocardiogram, to identify
Rhythm (verify AF)
LV hypertrophy
P-wave duration and morphology or fibrillatory waves
Preexcitation
Bundle-branch block
Prior MI
Other atrial arrhythmias
To measure and follow the R-R, QRS, and QT intervals in conjunction with
antiarrhythmic drug therapy
2. Transthoracic echocardiogram, to identify
Valvular heart disease
LA and RA size
LV size and function
Peak RV pressure (pulmonary hypertension)
LV hypertrophy
LA thrombus (low sensitivity)
Pericardial disease
3. Blood tests of thyroid, renal, and hepatic function
For a first episode of AF, when the ventricular rate is difficult to control
Additional testing
One or several tests may be necessary.
1. Six-minute walk test
If the adequacy of rate control is in question
2. Exercise testing
If the adequacy of rate control is in question (permanent AF)
To reproduce exercise-induced AF
To exclude ischemia before treatment of selected patients with a type IC
antiarrhythmic drug
3. Holter monitoring or event recording
If diagnosis of the type of arrhythmia is in question
As a means of evaluating rate control
4. Transesophageal echocardiography
To identify LA thrombus (in the LA appendage)
To guide cardioversion
5. Electrophysiological study
To clarify the mechanism of wide-QRS-complex tachycardia
To identify a predisposing arrhythmia such as atrial flutter or paroxysmal
supraventricular tachycardia
To seek sites for curative ablation or AV conduction block/modification
6. Chest radiograph, to evaluate
Lung parenchyma, when clinical findings suggest an abnormality
Pulmonary vasculature, when clinical findings suggest an abnormality
Type IC refers to the Vaughan Williams classification of antiarrhythmic drugs (see Appendix D). AF = atrial
fibrillation; AV = atrioventricular; LA = left atrial; LV = left ventricular; MI = myocardial infarction; RA = right
atrial; RV = right ventricular.
disease. Patients with persistent signs of LV dysfunction and/or signs of

myocardial ischemia are candidates for coronary angiography
Table 6 lists the clinical evaluation that may be necessary in patients with AF.
<<Table 6 >>
3.3 ECHOCARDIOGRAPHY
TTE should be performed in patients with AF:
o For whom a baseline echocardiogram is important for long-term
management.
o For whom a rhythm-control strategy that includes cardioversion
(electrical or pharmacological) is being considered.
o In whom there is a high risk or a suspicion of underlying
structural/functional heart disease (such as heart failure or heart
murmur) that influences their subsequent management (for
example, choice of antiarrhythmic drug)
o In whom refinement of clinical risk stratification for antithrombotic
therapy is needed.
In patients with AF who require anticoagulation therapy based on relevant clinical
criteria, TTE need not be routinely performed.
TOE should be performed in patients with AF:
o Where TTE is technically difficult and/or of questionable quality and
where there is a need to exclude cardiac abnormalities
o For whom TOE-guided cardioversion is being considered. (See
section 6.4.5, page 38)
3.4 CLINICAL FOLLOW-UP
The specialist caring for the AF patient should not only perform the baseline
assessment and institute the appropriate treatment, but also suggest a structured
plan for follow-up.
Important considerations during follow-up of the AF patient are listed below:
x Has the risk prole changed (e.g. new diabetes or hypertension), especially
with regard to the indication for anticoagulation?
x Is anticoagulation now necessaryhave new risk factors developed, or
has the need for anticoagulation passed, e.g. postcardioversion in a
patient with low thrombo-embolic risk?
x
Have the patients symptoms improved on therapy; if not, should other

therapy be considered?
Are there signs of proarrhythmia or risk of proarrhythmia; if so, should the

dose of an antiarrhythmic drug be reduced or a change made to another
therapy?
Has paroxysmal AF progressed to a persistent/permanent form, in spite of

antiarrhythmic drugs; in such a case, should another therapy be
considered?
x Is the rate control approach working properly; has the target for heart rate
at rest and during exercise been reached?
The diagnosis of AF requires documentation by ECG.2,10
10
In patients with suspected AF, an attempt to record an ECG should be made
dose of an antiarrhythmic drug be reduced or a change made to another

therapy?
x
Keypoints
Has paroxysmal AF progressed to a persistent/permanent form, in spite of

antiarrhythmic drugs; in such a case, should another therapy be
considered?
x Is the rate control approach working properly; has the target for heart rate
at rest and during exercise been reached?
I BIB
The diagnosis of AF requires documentation by ECG.2,10
I BIB
In patients with suspected AF, an attempt to record an ECG should be made

when symptoms suggestive of AF occur.2,14
I BIB
A simple symptom score (EHRA class) is recommended to quantify AF-related

symptoms.2,15
I CIC
All patients with AF should undergo a thorough physical examination, and a

cardiac- and arrhythmia-related history should be taken.
I BIB
In patients with severe symptoms, documented or suspected heart disease, or

risk factors, an echocardiogram is recommended.2,16,17
I CIC
In patients treated with antiarrhythmic drugs, a 12-lead ECG should be recorded

at regular intervals during follow-up.
IIaB
IIa B
In patients with suspected symptomatic AF, additional ECG monitoring should be

considered in order to document the arrhythmia.2,18
IIaB
IIa
B
Additional ECG monitoring should be considered for detection of silent AF in

patients who may have sustained an AF-related complication. 2,19
IIaC
IIa
C
In patients with AF treated with rate control, Holter ECG monitoring should be
considered for assessment of rate control or bradycardia.
IIa
C
IIaC
In young active patients with AF treated with rate control, exercise testing should
be considered in order to assess ventricular rate control.
IIaC
IIa
C
In patients with documented or suspected AF, an echocardiogram should be

considered.
IIaC
IIa
C
Patients with symptomatic AF or AF-related complications should be considered

for referral to a cardiologist.
IIaC
IIa C
A structured follow-up plan prepared by a specialist is useful for follow-up by a

general or primary care physician.
IIbB
IIb
B
In patients treated with rhythm control, repeated ECG monitoring may be

considered to assess the efficacy of treatment.2,20,21
IIbC
IIb C
Most patients with AF may benet from specialist follow-up at regular intervals.
<<Figure 3>>
11
12
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/ehq278)
Figure 3: Choice of rate and rhythm control strategies. Rate control is needed for most patients with AF unless the heart rate during AF is naturally slow. Rhythm
control may be added to rate control if the patient is symptomatic despite adequate rate control, or if a rhythm control strategy is selected because of factors such
as the degree of symptoms, younger age, or higher activity levels. Permanent AF is managed by rate control unless it is deemed possible to restore sinus rhythm
when the AF category is re-designated as long-standing persistent. Paroxysmal AF is more often managed with a rhythm control strategy, especially if it is
symptomatic and there is little or no associated underlying heart disease. Solid lines indicate the first-line management strategy. Dashed lines represent fall-back
objectives and dotted lines indicate alternative approaches which may be used in selected patients.
4. MANAGEMENT PRINCIPLES
4.1 GENERAL PRINCIPLES
In patients with AF or AFI, the aims of treatment involve the following five
objectives.
I
Relief of symptoms, such as palpitations, dizziness, fatigue and dyspnoea,

is paramount to the patient.
II. The prevention of serious complications, such as thromboembolism

(particularly ischaemic stroke) and heart failure, is equally important.
III. Optimal management of concomitant cardiovascular disease.
IV. Rate control.
V. Correction of rhythm disturbance.
These goals are not mutually exclusive and may be pursued simultaneously. The
initial strategy may differ from the long-term therapeutic goal.
A fundamental question to be answered for every patient with AF or AFI is
whether to obtain and maintain sinus rhythm by pharmacological or
nonpharmacological means (a rhythm-control strategy), or whether to aim
primarily to control heart rate rather than the rhythm (a rate-control strategy).
For patients with symptomatic AF lasting many weeks, initial therapy may be
anticoagulation and rate control while the long-term goal is to restore sinus
rhythm.
If rate control offers inadequate symptomatic relief, restoration of sinus rhythm
becomes a clear long-term goal. When cardioversion is contemplated and the
duration of AF is unknown or exceeds 48 h, anticoagulation will be necessary.
Early cardioversion may be necessary if AF causes hypotension or worsening
heart failure. In contrast, amelioration of symptoms by rate control in older
patients may steer the clinician away from attempts to restore sinus rhythm. In
some circumstances, when the initiating pathophysiology of AF is reversible, as
for instance in the setting of thyrotoxicosis or after cardiac surgery, no long-term
therapy may be necessary.
Regardless of the approach, the need for anticoagulation is based on stroke risk
and not on whether sinus rhythm is maintained.
For rate and rhythm control, drugs remain the first choice. Radiofrequency
ablation may be considered in symptomatic AF and in lone AF to avoid long-term
drug therapy. In selected individuals undergoing cardiac surgery, surgical maze
procedure may be a therapeutic option.
4.2 THROMBOEMBOLIC PROPHYLAXIS
Antithrombotic therapy must be considered in all patients with AF. Strategies that
may reduce thromboembolic risk include the following treatments:
13
Anticoagulants such as Vitamin K Antagonist,
For rate and rhythm control, drugs remain the first choice. Radiofrequency
ablation may be considered in symptomatic AF and in lone AF to avoid long-term
drug therapy. In selected individuals undergoing cardiac surgery, surgical maze
procedure may be a therapeutic option.
4.2 THROMBOEMBOLIC PROPHYLAXIS
Antithrombotic therapy must be considered in all patients with AF. Strategies that
may reduce thromboembolic risk include the following treatments:
Anticoagulants such as Vitamin K Antagonist,
Antiplatelet agents, such as aspirin and clopidogrel
Intravenous (IV) heparin or low molecular weight heparin (LMWH)
Left atrial appendage (LAA) occlusion, either surgically or percutaneously.
The decision regarding the method of reduction in the risk of stroke, should take
into account both the persons risk of thromboembolism and their risk of bleeding.
It is important to remember that vitamin K antagonist such as Warfarin is very
effective and reduces the risk of stroke overall by two thirds. (For details see
Section 6, page 26)
4.3. HEART RATE CONTROL VERSUS RHYTHM CONTROL
Rate control involves the use of chronotropic drugs or electrophysiological or
surgical interventions to reduce the rapid heart rate (ventricular rate) often found
in patients with AF. Although the atria continue to fibrillate with this strategy, it is
nonetheless thought to be an effective treatment as it improves symptoms and
reduces the risk of associated morbidity. However, the persistence of the
arrhythmia continues the risk of stroke and thromboembolic events occurring.
Administering antithrombotic drugs reduces this risk. (See Figure 3, page 12)
Rhythm control involves the use of electrical or pharmacological cardioversion or
electrophysiological or surgical interventions to convert the arrhythmia associated
with AF to normal sinus rhythm. Patients who have been successfully
cardioverted are generally administered antiarrhythmic drugs for the long term to
help prevent the recurrence of AF. The rhythm control strategies also require the
appropriate administration of antithrombotic therapy to reduce the risk of stroke
and thromboembolic events occurring.
Randomized trials comparing outcomes of rhythm versus rate control strategies
in patients with AF are summarized in Table 7 and 8.22-28
<<Table 7>>
<<Table 8>>
14
15
23
24
25
26
27
28
AFFIRM (2002)
RACE (2002)
STAF (2003)
HOTCAFE (2004)
AF-CHF (2008)
J-RHYTHM (2009)
823
1376
205
200
522
4060
252
Patients
(n)
64.7
66
60.8
66.0
68.0
69.7
61.0
Mean
age
(years)
1.6
3.1
1.7
1.6
2.3
3.5
1.0
Mean
follow-up
(years)
Paroxysmal AF
Persistent AF
(>4 weeks and
<2 years), LA size
>45 mm, CHF NYHA
IIIV, LVEF <45%
First clinically overt
persistent AF (>7 days
and <2 years),
age 5075 years
LVEF <35%, symptoms
of CHF, history of AF
(>6 h or
DCC <last 6 months)
Persistent AF or flutter for

<1 years and 12
cardioversions over 2
years and oral
anticoagulation
Persistent AF
(7360 days)
Paroxysmal AF or
persistent AF, age >65
years, or risk of stroke or
death
Inclusion criteria
182/1376
(27%)
175/1376
(25%)
89/405
(22.0%)
Cardiovascular death
Composite of total
mortality, symptomatic
cerebral infarction,
systemic embolism, major
bleeding, hospitalization for
heart failure, or physical/
psychological disability
64/418
(15.3%)
4/104
(3.9%)
1/101
(1.0%)
Composite: death,
thrombo-embolic events;
intracranial/major
haemorrhage
9/100
(9.0%)
60/266
(22.6%)
10/100
(10.0%)
44/256
(17.2%)
Composite: cardiovascular
death, CHF, severe bleeding,
pacemaker implantation,
thrombo-embolic events,
severe adverse effects of
antiarrhythmic drugs
356/2033
(26.7%)
Composite: overall
mortality, cerebrovascular
complications, CPR, embolic
events
310/2027
(25.9%)
0.012
0.59
> 0.71
0.99
0.11
0.08
Patients reaching primary

outcome (n)
Rate
Rhythm
P
control
control
76/125
70/127
0.32
(60.8%)
(55.1%)
All-cause mortality
Symptomatic improvement
Primary outcome parameter
AF = atrial fibrillation; AFFIRM = Atrial Fibrillation Follow-up Investigation of Rhythm Management; CHF = congestive heart failure; CPR = cardiopulmonary
resuscitation; DCC = direct current cardioversion; HOT CAFE = How to Treat Chronic Atrial Fibrillation; J-RHYTHM = Japanese Rhythm Management Trial for
Atrial Fibrillation; LVEF = left ventricular ejection fraction; NYHA = New York Heart Association; PIAF = Pharmacological Intervention in Atrial Fibrillation; RACE =
RAte Control versus Electrical cardioversion for persistent atrial fibrillation; STAF = Strategies of Treatment of Atrial Fibrillation.
22
Ref
PIAF (2000)
Trial
Table 7: General characteristic s of rhythm control and rate control trials in patients with AF
16
25
26
27
STAF (2003)
HOT CAF (2004)
AF-CHF (2008)
228/217
4 (1/3)
12 (8/4)
36
666 (310/356)
Death from all causes

(in rate/rhythm)
175/182
0/2
8/3
18/18
167/164
1/1
Deaths from
cardiovascular
causes
53/35
1/1
0/1
ND
113/165
11/9
0/3
1/5
ND
77/80
ND
Stroke
Deaths from noncardiovascular causes
ND
ND
ND
14/21
ND
ND
Thrombo-embolic
events
ND
5/8
8/1
12/9
107/96
ND
Bleeding
Total number of patients not reported.

AF = atrial fibrillation; AFFIRM = Atrial Fibrillation Follow-up Investigation of Rhythm Management; HOT CAFE = HOw to Treat Chronic Atrial Fibrillation; ND = not
determined; PIAF = Pharmacological Intervention in Atrial Fibrillation; RACE = RAte Control versus Electrical cardioversion for persistent atrial fibrillation; STAF =
Strategies of Treatment of Atrial Fibrillation.
23
24
RACE (2002)
22
PIAF (2000)
AFFIRM (2002)
Ref
Trial
Table 8: Comparison of adverse outcomes in rhythm control and rate control trials in patients with AF
The consistent nding in all ve studies was that rhythm control offered no
survival advantage and, in most cases, had little effect on morbidity and quality of
life. However, it should be emphasised that these conclusions are not necessarily
applicable to all groups of patients. The ve recent studies enrolled mostly older
patients with additional risk factors for stroke, many of whom also had heart
failure. Younger patients with normal hearts and primarily paroxysmal atrial
brillation (PAF) were not well represented. Importantly, in a predened subgroup
of AFFIRM participants aged less than 65 years, hazard ratios for death showed
a paradoxical trend towards superiority of the rhythm-control strategy.
The initial therapy after onset of AF should always include adequate
antithrombotic treatment and control of the ventricular rate. If the ultimate goal is
restoration and maintenance of sinus rhythm, rate control medication should be
continued throughout follow-up, unless continuous sinus rhythm is present. The
goal is to control the ventricular rate adequately whenever recurrent AF occurs.
The decision to add rhythm control therapy to the management of AF requires an
individual decision and should therefore be discussed at the beginning of AF
management. Before choosing rate control alone as a long-term strategy, the
clinician should consider how permanent AF is likely to affect the individual
patient in the future and how successful rhythm control is expected to be (Figure
3, page 12). Symptoms related to AF are an important determinant in making the
decision to opt for rate or rhythm control (e.g. globally assessed by the EHRA
score, Table 5, page 7), in addition to factors that may inuence the success of
rhythm control. The latter include a long history of AF, older age, more severe
associated cardiovascular diseases, other associated medical conditions, and
enlarged LA size.
A rate-control strategy should be the preferred initial option in the following
patients with persistent AF:
x Over 65 years old
x With coronary artery disease and/or left ventricular dysfunction
x With contraindications to antiarrhythmic drugs
x Unsuitable for cardioversion*
A rhythm-control strategy should be the preferred initial option in the following
patients with persistent AF:
x Those who are symptomatic
x Younger patients
x Those presenting for the first time with lone AF
x Those with AF secondary to a treated/corrected precipitant
Keypoints
IA
IA
Rate control should be the initial approach in elderly patients with AF and minor
symptoms (EHRA class 1).23,24,27
IBIB
Rhythm control is recommended in patients with symptomatic (EHRA class 2)

AF despite adequate rate control.2,21,29,30,31
IA
IA
Rate control should be continued throughout a rhythm control approach to

ensure adequate control of the ventricular rate during recurrences of AF. 23
IIaC
IIaC
Rhythm control as an initial approach should be considered in young

symptomatic patients in whom catheter ablation treatment has not been ruled
out.
IIaC
17 in patients with AF secondary to a trigger

Rhythm control should be considered
or substrate that has been corrected (e.g. ischaemia, hyperthyroidism).
AF despite adequate rate control.

IA
Rate control should be continued throughout a rhythm control approach to

ensure adequate control of the ventricular rate during recurrences of AF. 23
IIaC
Rhythm control as an initial approach should be considered in young

symptomatic patients in whom catheter ablation treatment has not been ruled
out.
IIac
IIaC
Rhythm control should be considered in patients with AF secondary to a trigger

or substrate that has been corrected (e.g. ischaemia, hyperthyroidism).
IIaB
IIaB
Rhythm control in patients with AF and AF-related heart failure should be

considered for improvement of symptoms.29,30,32
5. MANAGEMENT ACUTE-ONSET AF
5. MANAGEMENT ACUTE-ONSET AF
5.1 ACUTE AF IN HEMODYNAMICALLY UNSTABLE PATIENTS

5.1 ACUTE AF IN HEMODYNAMICALLY UNSTABLE PATIENTS
The majority of patients who present with AF are hemodynamically stable but
there is a small
group of
of patients
whopresent
are significantly
compromised
by the
onset
The majority
patients who
with AF are
hemodynamically
stable
but
of AF. These
hospitalization
urgent intervention
therepatients
is a smallrequire
group ofimmediate
patients who
are significantlyand
compromised
by the onset
to preventoffurther
deterioration.
AF. These
patients require immediate hospitalization and urgent intervention
to prevent further deterioration.
Those considered in this group are; 33

x
x
x
Those considered in this group are; 33
Those with a ventricular rate greater than 150 bpm

x Those
with pains,
a ventricular
With ongoing
chest
or rate greater than 150 bpm
With ongoing chest pains, or
Criticalxperfusion.
x Critical perfusion.
In these circumstances, the concerns regarding intervention in the absence of

In these circumstances, the concerns regarding intervention in the absence of
anticoagulation
and echocardiography are counterbalanced by the need for
anticoagulation and echocardiography are counterbalanced by the need for
urgent treatment.
urgent treatment.
5.1.1 ACUTE
CONTROL
5.1.1RATE
ACUTE
RATE CONTROL
It is important
to understand
that inthat
these
circumstances
the the
slow
onset
It is important
to understand
in these
circumstances
slow
onsetofof
digoxin makes
inappropriate
for useforinuse
thisin situation.
Patients
whose
digoxinit makes
it inappropriate
this situation.
Patients
whoseAFAFisis
associatedassociated
with thyrotoxicosis
will not
to any
measures
with thyrotoxicosis
will respond
not respond
to any
measuresuntil
untilthe
the
underlyingunderlying
thyroid disease
is first treated.
Patients
with with
accessory
pathway
such
thyroid disease
is first treated.
Patients
accessory
pathway
such
as the Wolff-Parkinson-White
(WPW)(WPW)
syndrome
are particularly
at risk
following
as the Wolff-Parkinson-White
syndrome
are particularly
at risk
following
of AF because
theypresent
can present
rapid
ventricularrates
rates
the onset the
of onset
AF because
they can
with with
very very
rapid
ventricular
(greater
bpm)
and
mayspecific
need specific
management.
(greater than
200 than
bpm)200
and
may
need
management.
Whenpresent
patients with
present
with unacceptably
high ventricular
primary
aimisis
When patients
unacceptably
high ventricular
raterate
the the
primary
aim
of rate control.
one of rateone
control.
AF with
slow ventricular
rates
may respond
to atropine
2 mg
i.v.),
many
AF with slow
ventricular
rates may
respond
to atropine
(0.5 (0.5
2 mg
i.v.),
butbut
many
patients with symptomatic bradyarrhythmia may require either urgent placement
patients with symptomatic bradyarrhythmia may require either urgent placement
of a temporary pacemaker lead in the right ventricle and/or cardioversion.
of a temporary pacemaker lead in the right ventricle and/or cardioversion.
Acute initiation of rate control therapy should usually be followed by a long-term
Acute initiation
of rate
controldetails
therapy
should
followed
by a7 on
long-term
rate control
strategy;
of drugs
and usually
doses arebegiven
in Section
page 66.
rate control strategy; details of drugs and doses are given in Section 7 on page 66.
Keypoints
In the acute setting in the absence of pre-excitation, i.v. administration of -
IA acute
blockers
calcium channeli.v.
antagonists
is recommended
to
In the
settingorinnon-dihydropyridine
the absence of pre-excitation,
administration
of the ventricular response
to AF,
exercising
caution in is
patients
with
blockers orslow
non-dihydropyridine
calcium
channel
antagonists
recommended
to
34
hypotension
or heart failure.
slow the ventricular
response
to AF, exercising caution in patients with
IBIB
IC
In the acute setting, i.v. administration of amiodarone is recommended to control

the heart rate in patients with AF and concomitant heart failure, or in the setting
of hypotension.35
In pre-excitation, preferred drugs 18
are class I antiarrhythmic drugs (See Appendix
D) or amiodarone.
hypotension or heart failure.34

In the acute setting, i.v. administration of amiodarone is recommended to control
the heart rate in patients with AF and concomitant heart failure, or in the setting
of hypotension.35
IB
ICIC
In pre-excitation, preferred drugs are class I antiarrhythmic drugs (See Appendix

D) or amiodarone.
IIIC
IIIC
When pre-excited AF is present, -blockers, non-dihydropyridine calcium

channel antagonists, digoxin, and adenosine are contraindicated.
<<Table 9>>
5.1.2 PHARMACOLOGICAL CARDIOVERSION
Table 9 : Intravenous pharmacological agents for acute control of ventricular rate in AF/AFL
In the presence
of other
abnormalities (e.g.
hypertensive
disease,
Commonly
Onsetcardiac
of
Commonly-used
Adverse
Limitationsheart
Commonlyusedheart
loadingdisease),
action
effects ventricular ratesused
oralstill
valvular
onset of maintenance
AF
with acceptable
may
dose (IV)
dose (IV)
maintenance
compromised cardiac function. While rate control is unlikely to bring about
clinical
dose for
longterm rate
improvement in these circumstances, there is a need for the restorationcontrol
of sinus
Beta-blockers rhythm.
Drug
Esmolol
0.5 mg/kg
(very shortover 1 min
acting) Pharmacological
5 min
0.05 to 0.2 mg/
Hypotension,
Negative
Oral
heart block,
inotropic
preparation
cardioversion ofkg/min
AF infusion
may be initiated
administration
bradycardia,by a bolus
effect
not available
asthma,
heart with antiarrhythmic drugs
of an antiarrhythmic drug. Although the conversion
rate
failure
is lower than with direct current cardioversion (DCCV), it does not require
Metoprolol conscious sedation or anesthesia, and may facilitate the choice
23.75 to 200
In people
of antiarrhythmic
mg/day
with heart
drug therapy to prevent recurrent AF.
(divided doses)
failure, lower
doses may
be advisable.
Most patients who undergo pharmacological cardioversionNegative

require continuous
medical supervision and ECG monitoring during the druginotropic
infusion and for a
effect
Propanolol
0.15mg/kg over 5
5 min
N/A
80 to 240
period afterwards
(usually about half the drug elimination half-life)mg/day
to (divided
detect
min
doses)
proarrhythmic events such as ventricular proarrhythmia, sinus node arrest,
or
atrioventricular block.
Calcium channel
blockers
Several
Diltiazem
agents are available for pharmacological cardioversion (see Table 10 on

Hypotension,
In people
120 to 360
page 20).
heart block,
with heart
mg/day
heart failure
failure, lower
doses may
be advisable.
Negative
inotropic
effect
common agent
<<Table 10>>
(once daily
longacting)
0.075 to 0.15
to 5 min
120 to 360 mg/
In clinical
practice, 3 amiodarone
isN/Athe most
used
in the
mg/kg over 2 min
day (divided
doses or once
management of patients presenting in AF with haemodynamic compromise,
as it
daily longappears to have a hybrid
effect
of
rapid
reduction
in
ventricular
rate
in
acting)most
34
hypotension
or heart
patients
with failure.
a proportion of these reverting to sinus rhythm over a longer period.
Other
Verapamil
Digoxin
IB
0.25 to 1.0
2 hr
0.125 to 0.25
Digoxin
over 20 min
(10 min to
4 hours)
infusion
back pain,
heart block,
N/A
0.0625 to 0.375
mg
toxicity, heart
mg/day
In the acute
setting,
i.v. administration of mg/day
amiodarone
is recommended to
control
<<Figure
4>>
block,
(individualise
bradycardia
the heart rate in patients with AF and concomitant heart
failure, or in thedosage)
setting
35
of hypotension.
Amiodarone
5 mg/kg
Variable
50 mg/hour
Hypotension,
N/A
100 to 200
mg/day
IC
In pre-excitation, preferred drugs are class I antiarrhythmic

drugs (See Appendix
phlebitis
D) or amiodarone.
IIIC
pre-excited AF is present, -blockers, non-dihydropyridine calcium

When
N/A = not available
Adapted from: Fuster V, Ryden LE, Asinger RW, et al.134
channel
antagonists, digoxin, and adenosine are contraindicated.
Note: Administration of beta-blockers together with IV verapamil is contraindicated.
<<Table 9>>
In the presence of other cardiac abnormalities (e.g. hypertensive heart disease,
valvular heart disease), onset of AF with acceptable ventricular rates may still
compromised cardiac function. While rate control is unlikely to bring about clinical
improvement in these circumstances, there is a need for the restoration of sinus
rhythm.
Pharmacological cardioversion of AF may be initiated by a bolus administration
of an antiarrhythmic drug. Although the 19
conversion rate with antiarrhythmic drugs
is lower than with direct current cardioversion (DCCV), it does not require

In the presence of other cardiac abnormalities (e.g. hypertensive heart disease,
valvular heart disease), onset of AF with acceptable ventricular rates may still
compromised cardiac function. While rate control is unlikely to bring about clinical
improvement in these circumstances, there is a need for the restoration of sinus
rhythm.
hypotension
or heart
failure.34 of AF may be initiated by a bolus administration
Pharmacological
cardioversion
of an antiarrhythmic drug. Although the conversion rate with antiarrhythmic drugs
In
acute
setting,
administration
of amiodarone
is recommended
to control
is the
lower
than
with i.v.
direct
current cardioversion
(DCCV),
it does not
require
the
heart rate
in patients
with AF and
heart
failure, of
or antiarrhythmic
in the setting
conscious
sedation
or anesthesia,
andconcomitant
may facilitate
the choice
35
of
hypotension.
drug
therapy to prevent recurrent AF.
In
pre-excitation,
preferred
drugs
are class I antiarrhythmic
drugs
(Seecontinuous
Appendix
Most
patients who
undergo
pharmacological
cardioversion
require
D)
or amiodarone.
medical
supervision and ECG monitoring during the drug infusion and for a
period afterwards (usually about half the drug elimination half-life) to detect
pre-excited
is as
present,
-blockers,
non-dihydropyridine
calcium
When
proarrhythmic
eventsAFsuch
ventricular
proarrhythmia,
sinus node arrest,
or
atrioventricular
block.digoxin, and adenosine are contraindicated.
channel
antagonists,
Several agents
<<Table
9>> are available for pharmacological cardioversion (see Table 10 on
page 20).
<<Table 10>>
Table
10: presence
Drug and doses
pharmacological
conversion of (recent-onset)
AF
In the
of for
other
cardiac abnormalities
(e.g. hypertensive
heart disease,
In clinical
practice,
amiodarone
is with
the acceptable
most common
agentrates
usedmay
in still
the
valvular
heart
disease),
onset of AF
ventricular
management
patients
presenting
AF control
withdose
haemodynamic
compromise,
as it
compromised
cardiac
function.
Whileinrate
is unlikely to bring
Drug of
Dose
Follow-up
Riskabout clinical
appears
to have
a 5hybrid
rapid
in
rate
in
most
Amiodarone
mg/kg
i.veffect
over 1h of 50mg/kg
Willof
slow
improvement
in these
circumstances,
there reduction
is a needPhlebitis,
for ventricular
thehypotension.
restoration
sinus
the ventricular
Delayedperiod.
AF
patients with a proportion of these reverting to sinus rhythm
over rate.
a longer
rhythm.
conversion to sinus rhythm.
Flecainide
200-300 mg p.o
N/A
Not suitable for patients with
<<Figure 4>> cardioversion of AF may be initiatedmarked
Pharmacological
by astructural
bolus administration
heart disease,
maywith
prolong
QRS duration, and
of an antiarrhythmic drug. Although the conversion rate
antiarrhythmic
drugs
hence theitQTdoes
interval;not
and may
is lower than with direct current cardioversion (DCCV),
require
inadvertently increase the
conscious sedation or anesthesia, and may facilitate the
choice
antiarrhythmic
ventricular
rateof
due
to conversion
drug therapy to prevent recurrent AF.
to atrial flutter and 1:1 conduction
to the ventricles.
Propafenone
mg p.o
Not suitable for patients with
Most
patients who 450-600
undergo
pharmacological cardioversion
require continuous
marked structural heart
medical supervision and ECG monitoring during the
drugmay
infusion
and for a
disease;
prolong QRS
duration; willhalf-life)
slightly slowto detect
period afterwards (usually about half the drug elimination
the ventricular
but may
proarrhythmic events such as ventricular proarrhythmia,
sinus rate,
node
arrest, or
inadvertently increase the
atrioventricular block.
ventricular rate due to conversion
to atrial flutter and 1:1 conduction
to the ventricles.
Several agents are available for pharmacological cardioversion
(see Table 10 on
page 20).
<<Table 10>>
In clinical practice, amiodarone is the most common agent used in the
management of patients presenting in AF with haemodynamic compromise, as it
appears to have a hybrid effect of rapid reduction in ventricular rate in most
patients with a proportion of these reverting to sinus rhythm over a longer period.
Adapted with modification from the ESC Guidelines for the Management of Atrial
<<Figure 4>>
Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/
ehq278)
20
21
oral flecainide
oral propefenone
i.v amiodarone
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010; doi:10.1093/eurheartj/ehq278)
Figure 4 Direct current conversion and pharmacological cardioversion of recent-onset AF in patients considered for pharmacological cardioversion. AF= atrial
fibrillation
No
Structural heart disease
Electrical cardioversion
Yes
No
Yes
Haemodynamic instability
Recent Onset AF (<48 h)
In suitable patients with recent-onset AF (generally <48 hours duration), a trial of

In suitable patients
with recent-onset
AFrhythm
(generally
hours duration),
a trial or
of
pharmacological
cardioversion
to sinus
can <48
be offered
with ecainide
pharmacological
cardioversion
to or
sinus
rhythm canstructural
be offered
with
ecainide
or
propafenone
(when
there is little
no underlying
heart
disease)
or i.v
In suitable patients with recent-onset AF (generally <48 hours duration), a trial of
propafenonepharmacological
(when there
or no to
underlying
structural
heart
disease)
i.v
amiodarone
thereiscardioversion
islittle
structural
disease)
(Figure
4, page
21). orThe
sinus
rhythm
can be offered
with ecainide
or
amiodaroneconversion
(when there
structural
4, heart
pagedisease)
21). The
anticipated
rate
isis50%
~15
120(Figure
min.
propafenone
(when
there
iswithin
little ordisease)
no underlying
structural
or i.v
anticipated conversion
is 50%
~15 disease)
120 min.(Figure 4, page 21). The
amiodarone rate
(when
there within
is structural
Inanticipated
suitable patients
with recent-onset
AF (generally
<48
hours duration), a trial of
conversion
rate is 50% within
~15 120
min.
pharmacological cardioversion to sinus rhythm can be offered with ecainide or
Keypoints
When
pharmacological
cardioversion
is or
preferred
and there
is no
structural
propafenone (when
there is little
no underlying
structural
heart
disease)heart
or i.v
When pharmacological
cardioversion
preferred
and there
is
structural
disease,
oral
ecainide
or propafenone
is isrecommended
forno4,
cardioversion
of
amiodarone
(when
there
is is
structural
disease)
(Figure
21).heart
The
When36-38
pharmacological
cardioversion
preferred
and
there is
nopage
structural
heart
IA
disease,
oral
ecainide
or
propafenone
is
recommended
for
cardioversion
of
anticipated
conversion
rateoris propafenone
50% within ~15
120 min.
recent-onset
AF.
disease,
oral
ecainide
is
recommended
for
cardioversion
of
recent-onsetrecent-onset
AF.36-38 AF.36-38
In patients with recent-onset AF and structural heart disease, i.v. amiodarone is
pharmacological
preferred
and disease,
there i.v.
is no
structural
heart
39-41
In patients
with recent-onset
andisstructural
i.v.
amiodarone
In
patients When
with
recent-onset
AFcardioversion
and AF
structural
heart heart
disease,
amiodarone
isis
recommended.
IAIA
39-41
disease,
or propafenone is recommended for cardioversion of
39-41 oral ecainide
recommended.
recommended.
36-38
recent-onset AF.
Digoxin (Level
of Evidence A), verapamil, sotalol, metoprolol (Level of Evidence
Digoxin (Level of Evidence A), verapamil, sotalol, metoprolol (Level of Evidence
IIIABC
Digoxin
of
Evidence
A),
verapamil,
(Level
ofin
Evidence
B),
other(Level
-blocking
agents
(Level
of
Evidence
C)metoprolol
are
converting
InB),
patients
with
recent-onset
AF
andsotalol,
structural
heart
disease,
i.v.inamiodarone
is
IIIABC
other
-blocking
agents
(Level
of
Evidence
C) ineffective
are
ineffective
converting
IA
39-41
recommended.
B), other
-blocking
agents
ofare
Evidence
C)recommended.
are ineffective in converting
recentonset
AF toonset
sinus
rhythm
notare
recommended.
recentAF
to (Level
sinusand
rhythm
and
not
recent- onset AF to sinus rhythm and are not recommended.
(Level
of Evidence
A), verapamil,
sotalol,
(Level of Evidence
patients
with
a life-threatening
deterioration
in haemodynamic
stability
Inwith
patientsDigoxin
a life-threatening
deterioration
in metoprolol
haemodynamic
stability
In IC
IC
IIIABC
B),following
other -blocking
(Level
of Evidence
arecardioversion
ineffective in should
converting
onsetagents
of AF,
emergency
electrical
be
with
a the
life-threatening
deterioration
inC)cardioversion
haemodynamic
stability
In patientsthe
following
onset
of
AF, emergency
electrical
should
be
recentonsetirrespective
AF to sinusof
rhythm
and areofnot
performed,
the duration
therecommended.
AF.
following the
onset ofof the
AF, duration
emergency
cardioversion should be
performed,
irrespective
of the electrical
AF.
performed,Inirrespective
of the
of the deterioration
AF.
patients
with
a duration
life-threatening
in haemodynamic stability
5.1.2.1
Pill-in-the-pocket
approach
IC
5.1.2.1 Pill-in-the-pocket
approach
following the onset
of AF, emergency electrical cardioversion should be
42
performed,
irrespective
ofapproach
the duration
of theto
AF.outpatient administration of oral
refers
The pill-in-the-pocket
5.1.2.1 Pill-in-the-pocket
approach
42 or propafenone (450 to 600 mg) to carefully selected
ecainide (200
to 300 mg)
refers to outpatient administration of oral
approach
42
patients
whose
initial therapy
in hospital
and well tolerated.
5.1.2.1
approach
refers
to outpatient
of oral
approach
ecainide
(200
to Pill-in-the-pocket
300
mg)
or
propafenone
(450
to was
600effective
mg)administration
to carefully
selected
ecainidewhose
(200
to
300
mg)
or
propafenone
to
600
mg)
to
carefully
selected
patients
initial
therapy
in
hospital
was
effective
and
well
tolerated.
42 (450
This
approach
could
be
considered
in
appropriately
selected
patients
who
of have
oral
The pill-in-the-pocket approach refers to outpatient administration
IIaB
patients whose
initial
insymptoms
hospital
effective
andtowell
tolerated.
infrequent
buttherapy
prolonged
ofwas
paroxysmal
AF (PAF).
ecainide
(200
to
300 mg)
or
propafenone
(450
to 600
mg)
carefully
selected
This
approach
could
be
considered
in
appropriately
selected
patients
who
have
patients
whose
initial
therapy
in
hospital
was
effective
and
well
tolerated.
Keypoints
There
is anbe
uncommon
probability
of AF reverting
to AFL with
this approach
and
This
approach
could
considered
appropriately
patients
who have
infrequent
but
prolonged
symptoms
ofinparoxysmal
AFselected
(PAF).
before
antiarrhythmic
medication
initiated,
a selected
beta-blocker,
diltiazem
or
This
approach
could
be considered
inisappropriately
patients
who have
infrequent
but
prolonged
symptoms
of paroxysmal
AF (PAF).
IIaB
IIaB
verapamil
should
be
given
to
prevent
rapid
AV
conduction.
but prolonged
symptoms
of paroxysmal
AF (PAF).
There is aninfrequent
uncommon
probability
of AF reverting
to AFL
with this approach and
There isantiarrhythmic
an uncommon
probability
ofbelow
reverting
with
thisanapproach
and
before
medication
isAFinitiated,
ato AFL
beta-blocker,
diltiazem
or
Patients
the
conditions
areAF
contraindicated
for such
approach:
There
is anwith
uncommon
probability
of
reverting to AFL
with this
approach and
before antiarrhythmic
medication
israpid
initiated,
a beta-blocker,
verapamil
should
be
given
tomore
prevent
AVinitiated,
conduction.
x Those
aged
than 75
years,
before
antiarrhythmic
medication
is
a beta-blocker,diltiazem
diltiazem or
or
verapamil should
beshould
given
to
prevent
rapid AV
x Those
withbe
AFgiven
duration
greater
thanconduction.
7AV
days,
verapamil
to prevent
rapid
conduction.
x
NYHA
Class
III
to
IV
or
signs
of
heart
failure
on
examination,
Patients with the conditions below are contraindicated for such an approach:
withthe
a mean
rate
than 70for
bpm,
Patients
with
conditions
below
are less
contraindicated
for such
approach:
Patients
with
thex AF
conditions
below
are
contraindicated
such
an an
approach:
x Those
aged
more
than
75ventricular
years,
Previous
myocardial
infarction
angina,
x xThose
aged
more
than
75
years,
aged
more
than
75
years,
x Those with
AF
duration
greater
than
7 or
days,
Valvular
disease,greater than 7 days,
x xThose
withheart
AF duration
Those with
AF
greater
days, on examination,
x NYHA
Class
IIIduration
to IV or signs
of than
heart7failure
Cardiomyopathy,
x xNYHA
Class III to IV or signs of heart failure on examination,
NYHA
III
to
IV
or
signs
of less
heartthan
failure on
examination,
x AF
withClass
ax mean
ventricular
rate
bpm,
xAF
Bundle
block,
with abranch
mean ventricular
rate less 70
than
70 bpm,
AF with axmyocardial
mean
ventricular
rate
than
70 bpm,
x Previous
infarction
orless
angina,
xPrevious
Known
sick
sinus syndrome,
myocardial
infarction
or angina,
x Previous
myocardial
infarction
Valvular xheart
disease,
Valvular
heart
disease, or angina,
Valvular xheart
disease,
Cardiomyopathy,
x Cardiomyopathy,
x Bundle
branch block,
Cardiomyopathy,
x Bundle
branch
block,
x Known
sick
sinus syndrome,
Bundle sick
branch
block,
x Known
sinus
syndrome,
x
Low
serum
potassium,
x Known sick sinus syndrome,
x Or renal or hepatic insufficiency.
With such an approach emergency room visits and hospitalization could

markedly be reduced.
IIaB
IIaB
In selected patients with recent-onset AF and no signicant structural heart

disease, a single high oral dose of ecainide or propafenone (the pill-in-thepocket approach) should be considered, provided this treatment has proven safe
during previous testing in a medically secure environment.42
5.1.3 DIRECT CURRENT CARDIOVERSION
22
DCCV is an effective method of converting AF to sinus rhythm. Successful DCCV

is usually dened as termination of AF, documented as the presence of two or
IaB
IaB
With such an approach emergency room visits and hospitalization could

In selected patients with recent-onset AF and no signicant structural heart
disease, a single high oral dose of ecainide or propafenone (the pill-in-thepocket approach) should be considered, provided this treatment has proven safe
during previous testing in a medically secure environment.42
5.1.3 DIRECT CURRENT CARDIOVERSION
DCCV is an effective method of converting AF to sinus rhythm. Successful DCCV
is usually dened as termination of AF, documented as the presence of two or
more consecutive P waves after shock delivery.
5.1.3.1 Procedure
x Low serum potassium,
x Oradequate
renal or hepatic
insufficiency.
Unless
anticoagulation
has been documented for 4 weeks or AF is 48
h from a denite onset, a TOE should be performed to rule out atrial thrombi (see
With such
an39).
approach emergency room visits and hospitalization could
Figure
9, page
A pacing catheter or external pacing pads may be needed if asystole or
In selected occurs.
patients with recent-onset AF and no signicant structural heart
bradycardia
disease, a single high oral dose of ecainide or propafenone (the pill-in-theEvidence
favours the
use be
of biphasic
external
debrillators
because
their lower
pocket approach)
should
considered,
provided
this treatment
hasofproven
safe
42
energy
requirements
greatersecure
efficacy
compared
with monophasic
during previous
testing inand
a medically
environment.
debrillators. Trials have demonstrated a signicant increase in the rst shock
success
rate ofCURRENT
DCCV for AF
when biphasic waveforms were used.
5.1.3 DIRECT
CARDIOVERSION
Currently,
conventional
used
for electrode
DCCV is antwo
effective
method of positions
converting are
AF tocommonly
sinus rhythm.
Successful
DCCV
placement
(see Figure
5). Several
studies
have shown
anteroposterior
is usually dened
as termination
of AF,
documented
as thethat
presence
of two or
43
electrode
placement
is more
than anterolateral placement. If initial
more consecutive
P waves
aftereffective
shock delivery.
shocks are unsuccessful for terminating the arrhythmia, the electrodes should be
repositioned
and cardioversion repeated.
5.1.3.1 Procedure
<<
Figure
5>> anticoagulation has been documented for 4 weeks or AF is 48
Unless
adequate
placement for DCCV
h Figure
from5: Patch/paddle
a denite
onset, a TOE should be performed to rule out atrial thrombi (see
Figure 9, page 39).
The recommended initial energy for synchronised cardioversion (see figure 6) is:
Sternal
A pacing
catheter or external pacing pads may be needed if asystole or
patch/paddle
bradycardia occurs.
Sternal patch
x 200J or greater with monophasic waveform
Evidence
favours
the use
biphasicwaveform
external debrillators because of their lower
x Apex100J
or greater
withofbiphasic
patch/paddle
energy requirements and greater efficacy compared with monophasic
x
10-50J
biphasic
waveform
for
AFL
debrillators. Trials have demonstrated a signicant increase in the rst shock
success rate of DCCV for AF when biphasic waveforms were used.
Currently, two conventional positions are commonly used for electrode
placement (see Figure 5). Several studies have shown that anteroposterior
electrode placement is more effective than anterolateral placement.43 If initial
Apex patch
shocks are unsuccessful for terminating the arrhythmia, the electrodes should be
repositioned and cardioversion repeated.
<< Figure 5>>
The recommended initial energy for synchronised cardioversion (see figure 6) is:
x
200J or greater with monophasic waveform
100J or greater with biphasic waveform
10-50J biphasic waveform for AFL

23
Figure 6 : ECG strip showing synchronized cardioversion
<< Figure 6>>

Outpatient/day care DCCV can be undertaken in patients who are
haemodynamically stable and do not have severe underlying heart disease. At
least 3 h of ECG and haemodynamic monitoring are needed after the procedure,
before the patient is allowed to leave the hospital.
Internal cardioversion may be helpful in special situations, e.g. when a patient
undergoes invasive procedures and cardioversion catheters can be placed
without further vascular access and when implanted debrillation devices are
present.
5.1.3.2 Complications
The risks and complications of cardioversion are associated primarily with
x Thrombo-embolic events,
x Post-cardioversion arrhythmias, and
x The risks of general anesthesia.
The procedure is associated with 1 2% risk of thromboembolism, which can be
reduced by adequate anticoagulation in the weeks prior to cardioversion or by
exclusion of left atrium thrombi before the procedure. Skin burns are a common
complication. In patients with sinus node dysfunction, especially in elderly
patients with structural heart disease, prolonged sinus arrest without an adequate
escape rhythm may occur. Dangerous arrhythmias, such as ventricular
tachycardia and brillation, may arise in the presence of hypokalaemia, digitalis
intoxication, or improper synchronization. The patient may become hypoxic or
hypoventilate from sedation, but hypotension and pulmonary oedema are rare.
5.1.3.3 Cardioversion in patients with implanted pacemakers and
debrillators
The electrode paddle should be at least 8 cm from the pacemaker battery, and
the antero-posterior paddle positioning is recommended. Biphasic shocks are
preferred because they require less energy for AF termination. In pacemakerdependent patients, an increase in pacing threshold should be anticipated. In the
absence of a pacemaker programmer, a pacing magnet may be placed over the
pacemaker generator pocket to provide temporary pacing support. These
patients should be monitored carefully. After cardioversion, the device should be
interrogated and evaluated to ensure normal function.
5.1.3.4 Recurrence after cardioversion
Recurrences after DCCV can be divided into three phases:
(1) Immediate recurrences, which occur within the rst few minutes after DCCV.
(2) Early recurrences, which occur during the rst 5 days after DCCV.
24
(3) Late recurrence, which occur thereafter.

Factors that predispose to AF recurrence are age, AF duration before
(3) Late recurrence, which occur thereafter.
cardioversion, number of previous recurrences, an increased LA size or reduced
LA function,Factors
and the
presence
of coronary
heart disease
or pulmonary
or mitral
that
predispose
to AF recurrence
are age,
AF duration
before
valve disease.
Atrial ectopic
with recurrences,
a long short
sequence,
faster
heart
cardioversion,
numberbeats
of previous
an increased
LA size
or reduced
rates, and variations
atrial
the risk
of AForrecurrence.
LA function,inand
theconduction
presence of increase
coronary heart
disease
pulmonary or mitral
Pre-treatment
with
antiarrhythmic
drugs
such
amiodarone,
sotalol, ecainide,
valve
disease.
Atrial ectopic
beats
withas
a long
short sequence,
faster heart
44-46
rates, and
variationsthe
in atrial
conduction
increase the
of AF
recurrence.
and propafenone
increases
likelihood
of restoration
ofrisk
sinus
rhythm.
withpatients
antiarrhythmic
drugs
as amiodarone,
sotalol,
Some highlyPre-treatment
symptomatic
in whom
AFsuch
occurs
infrequently
(e.g.ecainide,
once or
44-46
andstrongly
propafenone
increases
the likelihood
of restoration
of sinus as
rhythm.
twice a year)
prefer
to undergo
repeated
cardioversions
a long-term
Some
highly
symptomatic
patients
in
whom
AF
occurs
infrequently
(e.g.
once or
rhythm control strategy, rather than opting for rate control or other rhythm control
twice athey
year)may
strongly
to undergo repeated cardioversions as a long-term
modalities which
nd prefer
uncomfortable.
rhythm control strategy, rather than opting for rate control or other rhythm control
modalities which they may nd uncomfortable.
KeypointsDCCV is recommended when a rapid ventricular rate does not

Immediate
respond promptly
to pharmacological
measures
with AF rate
and does
ongoing
Immediate
DCCV is recommended
wheninapatients
rapid ventricular
not
myocardial
ischaemia,
symptomatic
hypotension,
angina,
or heart
ICIC
respond
promptly
to pharmacological
measures
in patients
withfailure.
AF and ongoing
Immediate DCCV is recommended for patients with AF involving pre-excitation

47
DCCV
is recommended instability
for patientsiswith
AF involving
pre-excitation
when
tachycardia
or haemodynamic
present.
IB rapid Immediate
47
IaB
Elective DCCV should be considered in order to initiate a long-term rhythm

Elective DCCV should be considered in order
to initiate a long-term rhythm
IIaB management
control
strategy for patients with AF. 41,43,48
IIaB
41,43,48
IaB
Pre-treatment
with amiodarone,
ecainide,
propafenone
or or
sotalol
should
Pre-treatment
with amiodarone,
ecainide,
propafenone
sotalol
should be
be
44-46
IIaB
44-46
considered
to enhance
of DCCV
and prevent
recurrent
AF.AF.
IIaB
considered
to success
enhance success
of DCCV
and prevent
recurrent
IbC
Repeated
DCCV
may
be considered
in highly
symptomatic
patients
refractory
Repeated
DCCV
may be considered
in highly
symptomatic
patients
refractory to
to
IIbC
IIbC
other therapy.
other therapy.
IbC
Pre-treatment
with -blockers,
diltiazem
or verapamil
consideredfor
forrate
rate
Pre-treatment
with -blockers,
diltiazem
or verapamil
maymay
be be
considered
IIbC
IIbC
control,the
although
the of
efficacy
these agents
in enhancing
success
DCCVor
or
control, although
efficacy
theseofagents
in enhancing
success
of ofDCCV
preventing
early recurrence
AF is uncertain.
preventing early
recurrence
of AF isofuncertain.
IIC
DCCV is contraindicated in patients with digitalis toxicity.
myocardial ischaemia, symptomatic hypotension, angina, or heart failure.
IB
when rapid tachycardia or haemodynamic instability is present.
control management strategy for patients with AF.
IIIC
IIIC
DCCV is contraindicated in patients with digitalis toxicity.
5.1.3 Antithrombotic therapy for acute-onset AF

Please go to section 6, page 26.
25
6. MANAGEMENT - PREVENTION OF THROMBOEMBOLISM

6.1 RISK STRATIFICATION FOR STROKE
Assessment of thromboembolic risk or risk stratification allows the clinician to
consider anticoagulant treatment for those people who are at an increased risk of
stroke.
Two recent systematic reviews have addressed the evidence base for stroke risk
factors in AF,49,50 and concluded that prior stroke/TIA/thrombo-embolism, age,
hypertension, diabetes, and structural heart disease are important risk factors.
The presence of moderate to severe LV systolic dysfunction TTE is the only
independent echocardiographic risk factor for stroke on multivariable analysis.
On TOE, the presence of LA thrombus, complex aortic plaques, spontaneous
echo-contrast and low LAA velocities are independent predictors of stroke and
thrombo-embolism.
Patients with paroxysmal AF should be regarded as having a stroke risk similar
to those with persistent or permanent AF, in the presence of risk factors.
Patients aged less than 60 years, with lone AF, i.e. no clinical history or physical
evidence of cardiovascular disease, carry a very low cumulative stroke risk,
estimated to be 1.3% over 15 years.
The various stroke clinical risk factors has led to publication of various stroke
schemes.51,52 The simplest risk assessment scheme is the CHADS2 score and as
shown in Table 11, has good stroke correlation. The CHADS2 [cardiac failure,
hypertension, age, diabetes, stroke (doubled)] risk index evolved from the AF
Investigators and Stroke Prevention in Atrial Fibrillation (SPAF) Investigators
criteria, and is based on a point system in which 2 points are assigned for a
history of stroke or TIA and 1 point each is assigned for age >75 years, a history
of hypertension, diabetes, or recent cardiac failure.51
The CHADS2 stroke risk stratication scheme should be used as an initial, rapid,
and easy-to-remember means of assessing stroke risk. In patients with a
CHADS2 score 2, chronic OAC therapy with a VKA is recommended in a doseadjusted approach to achieve an international normalized ratio (INR) target of 2.5
(range, 2.0 3.0), unless contraindicated.6,52
<<Table 11>>
A comparison of the 12 published risk-stratication49 schemes to predict stroke in
patients with non-valvular AF found that most had very modest predictive value
for stroke and the proportion of patients assigned to individual risk categories
varied widely across the schemes. The CHADS2 score categorized most subjects
as moderate risk. The choice of antithrombotic (anticoagulants or antiplatelets)
26
6.1 RISK STRATIFICATION FOR STROKE

Assessment of thromboembolic risk or risk stratification allows the clinician to
consider anticoagulant treatment for those people who are at an increased risk of
stroke.
Two recent systematic reviews have addressed the evidence base for stroke risk
49,50
that prior stroke/TIA/thrombo-embolism, age,
hypertension, diabetes, and structural heart disease are important risk factors.
The presence of moderate to severe LV systolic dysfunction TTE is the only
strokeanalysis.
rate
independent echocardiographic risk factor for strokeAdjusted
on multivariable
a
On TOE, the presence of LA thrombus,
spontaneous
Patientscomplex aortic plaques,
(%/year)
CHADS2 Score
echo-contrast
and low LAA velocities
are independent predictors of stroke and
(n=1733)
(95% confidence
thrombo-embolism.
concluded
factors
in AF,2 score and
Table
11: CHADS
and stroke
rate
interval)
Patients with paroxysmal AF should be regarded as having a stroke risk similar

to those with0 persistent or permanent
AF, in the presence of1.9
risk(1.2-3.0)
factors.
120
Patients aged
lone AF, i.e. no clinical history or physical
1 less than 60 years, with
2.8 (2.0-3.8)
463
evidence of cardiovascular disease, carry a very low cumulative stroke risk,
estimated to be 1.3% over 15 years.
523
4.0 (3.1-5.1)
The various stroke clinical risk factors has led to publication of various stroke
CHADS
schemes.51,52
2 score and as
3 The simplest risk assessment
(4.6-7.3)
337 scheme is the 5.9
shown in Table 11, has good stroke correlation. The CHADS2 [cardiac failure,
hypertension, age, diabetes, stroke (doubled)] risk index evolved from the AF
(6.3-11.1)
220
Investigators4 and Stroke Prevention
in Atrial Fibrillation8.5
(SPAF)
Investigators
criteria, and is based on a point system in which 2 points are assigned for a
history of stroke
years, a history
5 or TIA and 1 point each
12.5>75
(8.2-17.5)
65 is assigned for age
of hypertension, diabetes, or recent cardiac failure.51
used (10.5-27.4)
as an initial, rapid,
The CHADS62 stroke risk stratication 5scheme should be 18.2
and easy-to-remember means of assessing stroke risk. In patients with a
CHADS2 score 2, chronic OAC therapy with a VKA is recommended in a dosea
The adjusted
stroke rateto
was
derived from
the multivariablenormalized
analysis assuming
aspirin
usage;of
these
adjusted
approach
achieve
an international
rationo
(INR)
target
2.5
stroke rates are based on data from a cohort of hospitalized
AF patients, published in 2001, with low
6,52
(range,
2.0
3.0),
unless
contraindicated.
numbers in those with a CHADS2 score of 5 and 6 to allow an accurate judgement of the risk in these
patients. Given that stroke rates are declining overall, actual stroke rates in contemporary non51
hospitalized cohorts may also vary from these estimates. Adapted from Gage F et al. AF = atrial
<<TableCHADS
11>>2 = cardiac failure, hypertension, age, diabetes, stroke (doubled).
fibrillation;
A comparison of the 12 published risk-stratication49 schemes to predict stroke in

patients with non-valvular AF found that most had very modest predictive value
for stroke and the proportion of patients assigned to individual risk categories
varied widely across the schemes. The CHADS2 score categorized most subjects
as moderate risk. The choice of antithrombotic (anticoagulants or antiplatelets)
for the moderate risk group was at best uncertain.
Several published analyses 49,50,53-55 have found even patients at moderate risk
(currently dened as CHADS2 score =1, i.e. one risk factor) still derive signicant
benet from OAC over aspirin use, often with low rates of major haemorrhage.
Importantly, prescription of an antiplatelet agent was not associated with a lower
risk of adverse events.
Also, the CHADS2 score does not include many stroke risk factors, and other
stroke risk modiers need to be considered in a comprehensive stroke risk
assessment (see Table 11, page 27).
Rather than the use of the low, moderate, and high risk characterization that
only showed a modest predictive value, this guideline has adopted and recognize
that risk is a continuum. A risk factor-based approach for a more detailed stroke
risk assessment is encouraged for recommending the use of antithrombotic
therapy.
27
The risk factor-based approached for patients
with non-valvular AF have been
given an acronym, CHA2DS2VASc and the schema is based on two groups of
assessment (see Table 11, page 27).

Rather than the use of the low, moderate, and high risk characterization that
only showed a modest predictive value, this guideline has adopted and recognize
that risk is a continuum. A risk factor-based approach for a more detailed stroke
risk assessment is encouraged for recommending the use of antithrombotic
therapy.
The risk factor-based approached for patients with non-valvular AF have been
given an acronym, CHA2DS2VASc and the schema is based on two groups of
risk factors:
x
Major risk factors - prior history of stroke, TIA or thromboembolism

and/or age 75 or older
Clinically relevant non-major risk factors - hypertension, heart failure

(EF 40%), diabetes, age 6574 years, female gender, and vascular
disease (myocardial infarction, complex aortic plaques and PAD).
The risk may be calculated based on a point system in which 2 points are
allocated for each Major risk factors; and 1 point each is assigned for
Clinically relevant non major risk factors (see Table 11 on page 27).
6.2 STRATEGIES FOR THROMBOEMBOLIC PROPHYLAXIS
The CHADS2 stroke risk stratication scheme should be used as a simple initial
(and easily remembered) means of assessing stroke risk, particularly suited to
primary care doctors and non-specialists.
In patients with a CHADS2 score of 2, chronic OAC therapy, e.g. with a VKA, is
recommended in a dose adjusted to achieve an INR value in the range of 2.0
3.0, unless contraindicated.
In patients with a CHADS2 score of 0 1, or where a more detailed stroke risk
assessment is indicated, it is recommended to use a more comprehensive risk
factor-based approach incorporating other risk factors for thrombo-embolism (see
Table 12 and Figure 7).56-58
In all cases where OAC is considered, a discussion of the pros and cons with the
patient, and an evaluation of the risk of bleeding complications, ability to safely
sustain adjusted chronic anticoagulation, and patient preferences are necessary.
In some patients, for example, women aged less than 65 years with no other risk
factors (i.e. a CHA2DS2VASC score of 1) aspirin rather than OAC therapy may be
considered.
<<Table 12>>
<<Figure 7>>
28
Table 12. CHA2DS2VASC Score, stroke rate and approach to thromboprophylaxis in patients with AF
a) Risk Factors for Stroke and thrombo embolism in non-valvular AF

Major' risk factors
Clinically relevant non-major' risk

factors
Heart failure or moderate to
severe LV systolic dysfunction
(e.g, LV EF 40%)
Hypertension - Diabetes mellitus
Female sex - Age 65-74 years
Vascular diseasea
Previous stroke, TIA

or systemic embolism
Age 75 years
b) Risk factor-based approach expressed as a point based

scoring system, with the acronym CHA2DS2-VASc
(Note: maximum score is 9 since age may contribute 0,1 or 2 points)
Risk factor
Score
Congestive heart failure/LV dysfunction

1
Hypertension
1
Age 75
2
Diabetes mellitus
1
Stroke/TIA/thrombo-embolism
2
Vascular disease
1
Age 65-74
1
Sex category (i.e, female sex)
1
Maximum score
9
c) Adjusted stroke rate according to CHA2DS2-VASc score
CHA2DS2-VASC score
Patients (n=7329)
0
1
2
3
4
5
6
7
8
9
Adjusted stroke rate

b
(%/year)
1
422
1230
1730
1718
1159
679
294
82
14
0%
1.30%
2.20%
3.20%
4.00%
6.70%
9.80%
9.60%
6.70%
15.20%
Approach to thromboprophylaxis in patients with AF

Risk category
CHA2DS2-VASC
score
Recommended
antithrombotic therapy
One 'major' risk factor or 2

'clinically relevant non-major risk
factors
OAC
One 'clinically relevant non-major'

risk factor
Either OAC or aspirin 75325 mg daily. Preferred:

OAC rather than aspirin
No risk factors
Either aspirin 75-325mg

daily or no antithrombotic
therapy. Preferred: no
rather than aspirin
29
See text for definitions.

a
Prior myocardial infarction, peripheral artery disease, aortic plaque. Actual rates of stroke in contemporary
cohorts may vary from these estimates.
b
Based on Lip et al.54
AF=atrial fibrillation; EF =ejection fraction (as documented by echocardiography, radionuclide
ventriculography, cardiac catheterization, cardiac magnetic resonance imaging, etc.); LV=left ventricular;
TIA=transient ischaemic attack.
CHA2DS2-VASC=cardiac failure, hypertension, age 75 (doubled), diabetes, stroke (doubled)-vascular
disease, age 6574 and sex category (female); INR=international normalized ratio; OAC=oral
anticoagulation, such as a vitamin K antagonist (VKA) adjusted to an intensity range of INR 2.03.0 (target
2.5).
c
OAC, such as a VKA, adjusted to an intensity range of INR 2.03.0 (target 2.5). New OAC drugs, which
may be viable alternatives to a VKA, may ultimately be considered. For example, should both doses of
dabigatran etexilate receive regulatory approval for stroke prevention in AF, the recommendations for
thromboprophylaxis could evolve as follows considering stroke and bleeding risk stratification:
(a) Where oral anticoagulation is appropriate therapy, dabigatran may be considered, as an alternative to
adjusted dose VKA therapy. (i) If a patient is at low risk of bleeding (e.g. HAS-BLED score of 02; see Table
14 for HAS-BLED score definition), dabigatran 150 mg b.i.d. may be considered, in view of the improved
efficacy in the prevention of stroke and systemic embolism (but lower rates of intracranial haemorrhage and
similar rates of major bleeding events, when compared with warfarin); and (ii) If a patient has a measurable
risk of bleeding (e.g. HAS-BLED score of 3), dabigatran etexilate 110 mg b.i.d. may be considered, in view
of a similar efficacy in the prevention of stroke and systemic embolism (but lower rates of intracranial
haemorrhage and of major bleeding compared with VKA). (b) In patients with one clinically relevant nonmajor stroke risk factor, dabigatran 110 mg b.i.d. may be considered, in view of a similar efficacy with VKA
in the prevention of stroke and systemic embolism but lower rates of intracranial haemorrhage and major
bleeding compared with the VKA and (probably) aspirin. (c) Patients with no stroke risk factors (e.g.
CHA2DS2-VASC = 0) are clearly at so low risk, either aspirin 75325 mg daily or no antithrombotic therapy is
recommended. Where possible, no antithrombotic therapy should be
considered for such patients, rather than aspirin, given the limited data on the benefits of aspirin in this
patient group (i.e., lone AF) and the potential for adverse effects, especially bleeding.
CHADS2 score 2
No
+
+
Yes
Consider other risk factors*

Age 75 years
No
CHADS2 Score
Risk Factors
Congestive heart failure
Hypertension
Age 75
Diabetes
Stroke/TIA
Score
1
1
1
1
2
*Other clinically relevant nonmajor risk factor:

Age 65-74, female sex, vascular
disease
Yes
2 other risk factors*
Yes
No
OAC
1 other risk factor*
Yes
No
OAC (or aspirin)
Nothing (or aspirin)
Figure 7 Clinical flowchart for the use of oral anticoagulant for stroke prevention in AF. AF = atrial fibrillation; OAC = oral
anticoagulant; TIA = transient ischaemic attack.
7 Clinical flowchart for the use of oral anticoagulant for stroke prevention in AF. AF = atrial fibrillation; OAC = oral anticoagulant; TIA = transient ischaemic attack. A full
ption of theAdapted
CHADS2 from
can bethe
found
on page
?
ESC
Guidelines
for the Management of Atrial Fibrillation (2010 Version) (European heart Journal
2010; doi:10.1093/eurheartj/ehq278)
30
6.3 ANTITHROMBOTIC THERAPY

6.3.1 ANTICOAGULATION WITH VITAMIN K ANTAGONISTS
6.3 6ANTITHROMBOTIC
There were
large randomizedTHERAPY
trials, both primary and secondary prevention,
that provided an extensive and robust evidence base for VKA therapy in AF.
6.3.1 ANTICOAGULATION WITH VITAMIN K ANTAGONISTS
55
VKAtrials,
(international
normalized
ratio prevention,
[INR] 2-3)
In a meta-analysis
There were adjusted-dose
6 large randomized
both primary
and secondary
showed athat
significant
risk reduction
ofevidence
stroke and
risktherapy
reduction
provided 64%
an extensive
and robust
base26%
for VKA
in AF.of all
53,59-63
cause mortality in patients with non valvular AF.
In a meta-analysis55 adjusted-dose VKA (international normalized ratio [INR] 2-3)
showed a significant
64%was
risk reduction
of stroke 53,59-63
and 26%
risk reduction
of all
Risk of intracranial
hemorrhage
small (0.3-1.8%).
When
VKA is given
mortality
in patients
non valvular
AF.53,59-63
to elderlycause
patients
with
atrial with
fibrillation,
hypertension
must be managed
aggressively.
53,59-63
Risk of intracranial hemorrhage was small (0.3-1.8%).
When VKA is given
to elderly patients with atrial fibrillation, hypertension must be managed
IC
IIaA
Keypoints
Antithrombotic
therapy is recommended for patients with atrial utter as for those
aggressively.
with AF.
IC
IC
Antithrombotic therapy is recommended for patients with atrial utter as for those
with AF.
The selection
of antithrombotic therapy should be considered using the same
criteria irrespective of the pattern of AF (i.e. paroxysmal, persistent, or
The
selection of antithrombotic therapy should be considered using the same
49,50
permanent).
IIaA
IIaA
criteria irrespective of the pattern of AF (i.e. paroxysmal, persistent, or
permanent).49,50
IA
Antithrombotic therapy to prevent thrombo-embolism is recommended for all

patients with
AF, except
in those
at low risk
(lone AF, aged
<65 years, orforwith
Antithrombotic
therapy
to prevent
thrombo-embolism
is recommended
all
49,50,64
IA
IA
patients with
AF, except in those at low risk (lone AF, aged <65 years, or with
contraindications).
contraindications).49,50,64
IA
IA
IA
It is recommended that the selection of the antithrombotic therapy should be

It is recommended that the selection of the antithrombotic therapy should be
IA
based
the absolute risks of stroke/ thrombo-embolism
and bleeding, and
IA upon
based upon the absolute risks of stroke/49,50,51
thrombo-embolism and bleeding, and
the relative
and risk
benet
for a given
patient.
therisk
relative
and benet
for a given
patient.49,50,51
[cardiac
failure, failure,
hypertension,
age,age,
diabetes,
The
CHADS
hypertension,
diabetes,stroke
stroke(doubled)]
(doubled)]
The2 CHADS
2 [cardiac
IA
IA
is recommended
a simple
(easily
remembered) means
means of
score is score
recommended
as a as
simple
initialinitial
(easily
remembered)
51 AF. 51
assessing
stroke
risk
in
non-valvular
assessing stroke risk in non-valvular AF.
For the patients with a CHADS score of 2, chronic OAC therapy with a VKA is
IA
2, chronic
OAC therapy with a VKA is
ForIA
the patients
with a CHADS2 score2 ofregimen
recommended in a dose-adjusted
to achieve an INR range of 2.03.0
49,50,55
recommended
a dose-adjusted
regimen
to achieve an INR range of 2.03.0
(targetin
2.5),
unless contraindicated.
49,50,55
(target 2.5), unless contraindicated.
IA
IA
For a more detailed or comprehensive stroke risk assessment in AF (e.g. with
IA
IA
Patients with 1 major or > 2 clinically relevant non-major risk factors are high
risk, and OAC therapy is recommended, unless contraindicated.53
IA
CHADS
01), a risk factor-based
is recommended,
2 scores
For a more
detailed
or comprehensive
strokeapproach
risk assessment
in AF considering
(e.g. with
major and
clinically
non-major
stroke is
riskrecommended,
factors.53
CHADS2 scores
01),
a risk relevant
factor-based
approach
considering
53
major and clinically relevant non-major stroke risk factors.
IA
Patients with 1 major or > 2 clinically relevant non-major risk factors are high
53
risk, and OAC
therapy
is recommended,
contraindicated.
Patients
with one
clinically relevantunless
non-major
risk factor are at intermediate risk
and antithrombotic therapy is recommended, either as:
IA
IA
i. VKA therapy53 or
IB
IB
ii. aspirin 75325 mg daily50
IB
IB
IIaA
Patients with no risk factors are at low risk (essentially patients aged <65 years
with lone AF, with none of the risk factors) and the use of either aspirin 75325
mg daily or no antithrombotic therapy is recommended.53
Most patients with one clinically
31 relevant non-major risk factor should be
considered for OAC therapy (e.g. with a VKA) rather than aspirin, based upon an
assessment of the risk of bleeding complications, the ability to safely sustain
IA
IB
IA
or
VKA therapy therapy
andi.antithrombotic
is recommended, either as:
ii. aspirin 75325 mg daily50
i. VKA therapy53 or
IB
IB
50 at low risk (essentially patients aged <65 years

Patients
with75325
no risk mg
factors
ii. aspirin
dailyare
with lone AF, with none of the risk factors) and the use of either aspirin 75325
mg daily or no antithrombotic therapy is recommended.53
IB
Most
patients
withnone
oneofclinically
relevantand
non-major
factor
should
be
with lone
AF, with
the risk factors)
the use ofrisk
either
aspirin
75325
IIaA
53 aspirin, based upon an
IIaA
considered
for antithrombotic
OAC therapy (e.g.
withisa recommended.
VKA) rather than
mg daily or no
therapy
assessment of the risk of bleeding complications, the ability to safely sustain
49,50
adjusted
chronicwith
anticoagulation,
andrelevant
patient preferences.
Most
patients
one clinically
non-major risk factor should be
IIaA
considered for OAC therapy (e.g. with a VKA) rather than aspirin, based upon an
Anticoagulation
withrisk
VKAof isbleeding
also recommended
forthe
patients
more sustain
than 1
assessment
of the
complications,
ability with
to safely
IA
IA
moderatechronic
risk factor
(female gender,
between
65-74, 49,50
hypertension, diabetes
adjusted
anticoagulation,
and age
patient
preferences.
mellitus, vascular disease, HF, or impaired LV systolic function [ejection fraction
3,4,65
35%
or less or fractional
shortening
less than 25%]).
Anticoagulation
with VKA
is also recommended
for patients with more than 1
IA
moderate risk factor (female gender, age between 65-74, hypertension, diabetes
6.3.2 OPTIMAL
INTERNATIONAL
NORMALIZED
RATIO
mellitus,
vascular disease,
HF, or impaired
LV systolic function [ejection fraction
35% or less or fractional shortening less than 25%]).3,4,65
The level of anticoagulation is expressed as the INR and is derived from the ratio between
the actual
prothrombin
time and thatNORMALIZED
of a standardized
control serum.
6.3.2
OPTIMAL
INTERNATIONAL
RATIO
patients with is
non-valvular
it isINR
recommended
thatfrom
the target
intensity
of
TheIA
level ofFor
anticoagulation
expressed AF,
as the
and is derived
the ratio
between
anticoagulation
VKA
to maintain
anserum.
INR range of 2.0-3.0 (target
the actual prothrombin
timewith
and athat
of ashould
standardized
control
Keypoints
49,50,64
Patients
with one clinically relevant non-major risk factor are at intermediate risk
2.5)
and
therapy is recommended,
either as: that the target intensity of
Forantithrombotic
patients with non-valvular
AF, it is recommended
For patients withwith
AF awho
have
mechanical
heartan
valves,
it is recommended
that
anticoagulation
VKA
should
to maintain
INR range
of 2.0-3.0 (target
49,50,64 intensity of anticoagulation with a VKA should be based on the type
the target
IB
2.5)
53
IA
i. VKA
therapy
and
position
of theorprosthesis, maintaining an INR of at least 2.5 in the mitral
position
and at
least
an aortic
valve.64,66
For
patients
with
AF 2.0
whoforhave
mechanical
heart valves, it is recommended that
IB
IB
ii.
aspirin
75325
mganticoagulation
daily50
the target intensity of
with a VKA should be based on the type
IB
<<Figure
8>>
and position of the prosthesis, maintaining an INR of at least 2.5 in the mitral
position and at least 2.0 for an aortic valve.64,66
IB
Figure 8:
8: Adjusted
Adjusted
odds
ratios
for
ischaemic
stroke
and
intracranial
bleeding
in relation
relation
to intensity
intensity
of
A target
INR
of 2.5
(target
range
2.0 intracranial
to and
3.0) the
is safe
prevention
in
with
lone
AF,
with
none
of the
riskoffactors)
usefor
of primary
either
aspirin
75325
<<Figure
8>>
Figure
odds
ratios
for
ischaemic
stroke
and
bleeding
in
to
of
53 67 atrial fibrillation.
anticoagulation
in
randomised
trials
of
for
IA
older
more
than
75 years,
unless
contraindicated.
mg
daily
or no antithrombotic
therapy
istherapy
recommended.
anticoagulation
in patients
randomised
trials
of antithrombotic
antithrombotic
therapy
for people
people with
with atrial fibrillation.
IA
IA
Figure 8: Adjusted odds ratios for ischaemic stroke and intracranial bleeding in relation to intensity of
anticoagulation
inmajor
randomised
trials
of antithrombotic
therapy
for
people
atrial
fibrillation.
The
bleeding
rate
for
5 randomized
trials
was
1.2%
per
year. Inbe
2
A target
INR
ofwith
2.5
(target
range
ofrelevant
2.0
to clinical
3.0)
is
safe with
for
primary
prevention
in
Most
patients
one
clinically
non-major
risk
factor
should
IIaAIA
IA
time-dependent
INR
of
in 67
elderlybased
AF upon
cohorts,
older patients
more
thananalyses
75 years,
unless
contraindicated.
considered
for OAC
therapy
(e.g. with
aanticoagulation
VKA)
rather than
aspirin,
an
intracranial bleed
with INRcomplications,
values over 3.5
4.0, and
there was
no
assessment
of theincreased
risk of bleeding
thetoability
to safely
sustain
49,50
The major
bleeding
rate for 5 randomized
trials was 1.2% per year. In 2
adjusted
chronic
anticoagulation,
and patientclinical
preferences.
time-dependent INR analyses of anticoagulation in elderly AF cohorts,
intracranial bleed
increased
with INR
values overfor
3.5patients
to 4.0, and
Anticoagulation
with
VKA is also
recommended
with there
more was
thanno1
moderate risk factor (female gender, age between 65-74, hypertension, diabetes
mellitus, vascular disease, HF, or impaired LV systolic function [ejection fraction
35% or less or fractional shortening less than 25%]).3,4,65
6.3.2 OPTIMAL INTERNATIONAL NORMALIZED RATIO

The level of anticoagulation is expressed as the INR and is derived from the ratio between
the actual prothrombin time and that of a standardized control serum.
IA
IB
For patients with non-valvular AF, it is recommended that the target intensity of
anticoagulation with a VKA should to maintain an INR range of 2.0-3.0 (target
2.5) 49,50,64
For patients with AF who have mechanical heart valves, it is recommended that
the target intensity of anticoagulation with a VKA should be based on the type
and position of the prosthesis, maintaining an INR of at least 2.5 in the mitral
Reproduced
Reproduced with
with permission
permission from
from Ann
Ann Intern
Intern Med.
Med. Hylek
Hylek E,
E, Singer
Singer D.
D. Risk
Risk factors
factors for
for intracranial
intracranial
hemorrhage
in
<<Figure
8>> taking
hemorrhage
in outpatients
outpatients
taking warfarin.
warfarin. Ann
Ann Intern
Intern Med
Med 1994;120:897-902.
1994;120:897-902.
Reproduced with permission from Ann Intern Med. Hylek E, Singer D. Risk factors for intracranial
hemorrhage in outpatients taking warfarin. Ann Intern Med 1994;120:897-902.
IA
IA
A target INR of 2.5 (target range of 2.0 to 3.0) is safe for primary prevention in
older patients more than 75 years, unless contraindicated.67
The major bleeding rate for 5 randomized clinical trials was 1.2% per year. In 2
32 values over 3.5 to 4.0, and there was no
intracranial bleed increased with INR

<<Figure 8>>
IA
A target INR of 2.5 (target range of 2.0 to 3.0) is safe for primary prevention in
older patients more than 75 years, unless contraindicated.67
The major bleeding rate for 5 randomized clinical trials was 1.2% per year. In 2
intracranial bleed increased with INR values over 3.5 to 4.0, and there was no
increment with values between 2.0 and 3.0 compared with lower INR levels. (See
Figure 6, page 24)
For guide of using VKA in daily practice please refer to Appendix C, page 74.
6.3.2.1 Point-of-care
testing
and self-monitoring
of anticoagulation
increment with values
between
2.0 and 3.0 compared
with lower INR levels. (See
increment
with 24)
values between 2.0 and 3.0 compared with lower INR levels. (See
Figure 6, page
Figure 6, page 24)
Self-monitoring may be considered if preferred by a patient who is both physically

For guideable
of using
VKA in daily
practice please refer
Appendix
C, a
page
74.
and cognitively
to perform
the self-monitoring
test,to
if not,
designated
For guide of using
VKA in daily
practice please refer
to and,
Appendix
C, page
74.
carer could help. Appropriate training by a competent healthcare professional is
6.3.2.1 Point-of-care testing and self-monitoring of anticoagulation
6.3.2.1
testingremain
and self-monitoring
ofaanticoagulation
important,
and Point-of-care
the patient should
in contact with
named clinician.
These point-of-care
may alsoif be
usefulbyin
remote
places
allow
Self-monitoringdevices
may be considered
preferred
a patient
who
is both and
physically
be
considered
preferreddevices
by a test,
patient
who
is both
physically
patients Self-monitoring
easy
access may
to testing.
Point-of-care
also
adequate
and
cognitively
able
to perform
the ifself-monitoring
and,
ifrequire
not,
a designated
and
cognitively
able
to
perform
the
self-monitoring
test,
and,
if
not,
a
designated
quality assurance
carer couldand
help.calibration.
Appropriate training by a competent healthcare professional is
carer
couldand
help.
training
byina contact
competent
professional is
important,
theAppropriate
patient should
remain
withhealthcare
a named clinician.
important,
and the patient
should
in
a named
clinician.
These point-of-care
devices
mayremain
also THROMBIN
becontact
useful with
in INHIBITORS
remote
places
and allow
6.3.3 ANTICOAGULATION
WITH DIRECT
These
may Point-of-care
also be useful
in remote
allow
patientspoint-of-care
easy accessdevices
to testing.
devices
also places
require and
adequate
patients
easy access
to testing. Point-of-care devices also require adequate
quality assurance
and calibration.
Dabigatran
etexilate
is and
an calibration.
oral prodrug that is rapidly converted by a serum
quality
assurance
esterase6.3.3
to dabigatran,
a potent, WITH
direct,DIRECT
competitive
inhibitor
of thrombin. It does
ANTICOAGULATION
THROMBIN
INHIBITORS
6.3.3
ANTICOAGULATION
DIRECT
INHIBITORS
not require
regular
monitoring andWITH
has a
serumTHROMBIN
half-life of 12
to 17 hours.
Dabigatran etexilate is an oral prodrug that is rapidly converted by a serum
Dabigatran
etexilate is aanpotent,
prodrug
that is rapidly
converted
by a. Itserum
does
esterase to dabigatran,
direct, competitive
inhibitor
of
thrombin
The Randomized
Evaluation of oral
Long-term
Anticoagulation
Therapy
(RE-LY)
. It does
esterase
to regular
dabigatran,
a potent,
direct,
inhibitor
of 17
thrombin
not require
monitoring
and
hasfixed
a competitive
serum
half-life
of
12 to
hours.
was a randomized
trial
comparing
two
doses
of
dabigatran,
given in a
not require regular monitoring and has a serum half-life of 12 to 17 hours.
blinded manner, with open-label use of VKA in patients with atrial fibrillation.58
The Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY)
Dabigatran
110
mg b.i.d. was non-inferior
to VKA for the prevention
of
stroke
The
Randomized
of Long-term
Therapygiven
(RE-LY)
was a
randomizedEvaluation
trial comparing
two fixedAnticoagulation
doses of dabigatran,
in a
and systemic
with
lower rates
offixed
major
bleeding,
whilst dabigatran
was
a embolism
randomized
comparing
of dabigatran,
given in 58
a
blinded
manner, withtrial
open-label
usetwo
of VKA
indoses
patients
with atrial fibrillation.
58
blinded
withb.i.d.
open-label
uselower
of VKA
in
patients
with
atrial
fibrillation.
150 mgDabigatran
b.i.d. manner,
was
of the
stroke
and
systemic
110 associated
mg
waswith
non-inferior
torates
VKA
for
prevention
of
stroke
Dabigatran
110
mg
b.i.d.
was
non-inferior
to
VKA
for
the
prevention
of
stroke
embolism
with
similarembolism
rates of with
major
haemorrhage,
compared
and
systemic
lower
rates of major
bleeding, with
whilstVKA.
dabigatran
and
with lowerwith
rates
of major
whilst
150 systemic
mg b.i.d.embolism
was associated
lower
ratesbleeding,
of stroke
anddabigatran
systemic
150
mg b.i.d.
was associated
with
lower ratescompared
of strokewith
and
systemic
embolism
with similar
rates of major
haemorrhage,
VKA.
embolism with similar rates of major haemorrhage, compared with VKA.
IB
Where oral anticoagulation is appropriate therapy for patients with non-valvular

Keypoints
AF, dabigatran may be considered, as an alternative to adjusted dose VKA
Where oral anticoagulation is appropriate therapy for patients with non-valvular
therapy.
Where
oral anticoagulation
is appropriate
therapy
for patients
with non-valvular
IB
AF, dabigatran
may be considered,
as an
alternative
to adjusted
dose VKA
IBIB
AF, dabigatran may be considered, as an alternative to adjusted dose VKA
therapy.
There is therapy.
currently no evidence to support the use of dabigatran for AF associated
with valve
disease,
prosthetic
valve,toinsupport
pregnancy
and
renal
failure.
There
is currently
no evidence
the use
of chronic
dabigatran
for AF
associated
IB
There
is currently
evidencevalve,
to support
the use of
dabigatran
for AF
associated
with
valve
disease,noprosthetic
in pregnancy
and
chronic renal
failure.
with valve disease, prosthetic valve, in pregnancy and chronic renal failure.
Patients with AF who are indicated for OAC but are unwilling to go on VKA
Patients
with AF who arechronic
indicated
OAC but are therapy
unwillingwith
to go
on VKA
because
of the inconvenience,
oralfor
anticoagulant
dabigatran
IB
Patients
with
AF
who are indicated
for
but are unwilling
to go
on VKA
because
of
the
inconvenience,
chronic
oralOAC
anticoagulant
therapy with
dabigatran
IBIBmg twice
150
daily
may
be considered,
unless
because
of the
inconvenience,
chronic
oral contraindicated.
anticoagulant therapy with dabigatran
150 mg twice daily may be considered, unless contraindicated.
150 mg twice daily may be considered, unless contraindicated.
IC
Where patients
are at are
a higher
risk of
(HAS-BLED
110
Where patients
at a higher
riskbleeding
of bleeding
(HAS-BLEDt3),
t3),dabigatran
dabigatran 110
IC
Where
patients
are
at considered,
a higherunless
riskunless
of contraindicated.
bleeding
(HAS-BLED t3), dabigatran 110
mg
daily
may
bemay
considered,
twice
daily
be
contraindicated.
ICICtwicemg
mg twice daily may be considered, unless contraindicated.
There
was however
an increase
in rate
the rate
of gastrointestinalbleeding
bleeding with
There was
however
an increase
in the
of gastrointestinal
with the
the
There was however an increase in the rate of gastrointestinal bleeding with the
higher dose of dabigatran, despite an overall lower rates of bleeding at other

sites.
IA
IA
Antithrombotic agent should be chosen based upon the absolute risks of stroke
and bleeding and the relative risk and benefit for a given patient.
33
6.3.4 INVESTIGATIONAL AGENTS
higher dose of dabigatran, despite an overall lower rates of bleeding at other

sites.
Antithrombotic agent should be chosen based upon the absolute risks of stroke
and bleeding and the relative risk and benefit for a given patient.
6.3.4 INVESTIGATIONAL AGENTS
Several new anticoagulant drugs-broadly in two classes, another oral direct
thrombin inhibitors (e.g. AZD0837) and the oral factor Xa inhibitors (rivaroxaban,
apixaban, edoxaban, betrixaban, YM150, etc.)-are being developed for stroke
prevention in AF.
6.3.5 ANTIPLATELET AGENT ASPIRIN
Aspirin has been perceived to be safer than VKA in AF patients, but recent trials
have shown that VKA are substantially more effective than aspirin for stroke
prevention, with no difference in major bleeding event rates between VKA and
aspirin treated patients.55,68
In seven primary prevention trials, treatment with aspirin was associated with a
non-signicant 19% reduction in the incidence of stroke. There was an absolute
risk reduction of 0.8% per year for primary prevention trials and 2.5% per year for
secondary prevention by using aspirin. When data from all comparisons of
antiplatelet agents and placebo or control groups were included in the metaanalysis, antiplatelet therapy reduced stroke by 22%.55
The magnitude of stroke reduction from aspirin vs. placebo in the meta-analysis
is broadly similar to that seen when aspirin is given to vascular disease subjects.
Given that AF commonly co-exists with vascular disease, the modest benet
seen for aspirin in AF is likely to be related to its effects on vascular disease.
In the Japan Atrial Fibrillation Stroke Trial,69 patients with lone AF were
randomized to an aspirin group (aspirin at 150 200 mg/day) or a placebo
control group. The primary outcomes of cardiovascular death and non fatal
stroke or TIA was 3.1% per year in the aspirin group and was worse than those
in the control group, 2.4% per year, and treatment with aspirin caused a nonsignicant increased risk of major bleeding (1.6%) compared with control (0.4%).
The Birmingham Atrial Fibrillation Treatment of the Aged (BAFTA) study also
showed that VKA (target INR 2 3) was superior to aspirin 75 mg daily in
reducing the primary endpoint of fatal or disabling stroke, intracranial
hemorrhage, or thromboembolism by 52%, with no difference in the risk of major
hemorrhage between VKA and aspirin.68
6.3.6 ASPIRIN AND CLOPIDOGREL COMBINATION
In patients with non valvular AF, adjusted dose VKA was found to be superior to
the combination of clopidogrel (75mg daily) plus aspirin (75-100 mg daily) for the
prevention of first occurrence of stroke, non-CNS systemic embolism, myocardial
infarction and vascular death.56
However, clopidogrel (75mg daily) plus aspirin (75-100 mg daily) conferred a
relative risk reduction of 11% compared to aspirin.57
There was an increased risk of major bleeding in patients receiving clopidogrel
plus aspirin compared to patients receiving aspirin alone and was broadly similar
to that seen with VKA.57
Combination therapy with aspirin 75100 mg plus clopidogrel 75 mg daily, should
be considered for stroke prevention in patients for whom there is patient refusal
34
to take OAC therapy or a clear contraindication
to OAC therapy (e.g. inability to
cope or continue with anticoagulation monitoring), where there is a low risk of
However, infarction
clopidogrel
(75mg death.
daily) 56plus aspirin (75-100 mg daily) conferred a
and vascular
relative risk reduction of 11% compared to aspirin.57
However, clopidogrel (75mg daily) plus aspirin (75-100 mg daily) conferred a
57
risk reduction
compared
to aspirin.
There wasrelative
an increased
riskofof11%
major
bleeding
in patients receiving clopidogrel
plus aspirin
compared
to
patients
receiving
aspirin
alone and was broadly similar
There was an57increased risk of major bleeding in patients receiving clopidogrel
to that seen
VKA.
pluswith
aspirin
compared to patients receiving aspirin alone and was broadly similar
to that seen with VKA.57
IIaB
Keypoints
Combination therapy with aspirin 75100 mg plus clopidogrel 75 mg daily, should
Combination
therapy
with aspirin
clopidogrel
mg daily,refusal
should
be considered
for stroke
prevention
in 75100
patientsmgforplus
whom
there 75
is patient
IIaB
be considered
in patients
for whom
there(e.g.
is patient
refusal
toIIaB
take OAC
therapy orfora stroke
clear prevention
contraindication
to OAC
therapy
inability
to
to take OAC
or a clear contraindication
to OACthere
therapy
inability
to
cope or continue
withtherapy
anticoagulation
monitoring), where
is (e.g.
a low
risk of
cope or continue with anticoagulation monitoring), where there is a low risk of
57
bleeding.
57
bleeding.
IIbC
In some patients
with onewith
clinically
relevant
non-major
riskrisk
factor,
In some patients
one clinically
relevant
non-major
factor,e.g.,
e.g.,female
female
IIbC
IIbC
patients
aged
<65
years
other
risk factors,
aspirin
may
patients
aged
<65with
yearsnowith
no other
risk factors,
aspirin
maybebeconsidered
considered
rather
OAC therapy.
rather than
OACthan
therapy.
IN SPECIAL
CIRCUMSTANCES
6.4 ANTICOAGULATION
IN SPECIAL
CIRCUMSTANCES
6.4 ANTICOAGULATION
6.4.1 PERIOPERATIVE ANTICOAGULATION
6.4.1 PERIOPERATIVE ANTICOAGULATION
Patients with AF who are anticoagulated will require temporary interruption of
Patients with
who are
anticoagulated
will require
temporary
interruption
of
VKA AF
treatment
before
surgery or an invasive
procedure.
Many surgeons
require
VKA treatment
surgery
anINR
invasive
procedure.
surgeons
require
an INRbefore
less than
1.5 or or
even
normalization
beforeMany
undertaking
surgery.
The
riskthan
of clinically
even among
undergoing
an INR less
1.5 or signicant
even INR bleeding,
normalization
beforeoutpatients
undertaking
surgery.minor
The
procedures,
should be
weighed even
against
the riskoutpatients
of stroke andundergoing
thrombo-embolism
risk of clinically
signicant
bleeding,
among
minor
in
an
individual
patient
before
the
administration
of
bridging
anticoagulant
procedures, should be weighed against the risk of stroke and thrombo-embolism
therapy. (see Appendix C.1.9, page 80)
in an individual patient before the administration of bridging anticoagulant
therapy. (see
pagewhich
80) has a half-life of 36 42 h, treatment should
If theAppendix
VKA usedC.1.9,
is warfarin,
be interrupted for about 5 days before surgery (corresponding approximately to
If the VKAve
used
is warfarin,
which has a half-life of 36 42 h, treatment should
half-lives
of warfarin),
be interrupted for about 5 days before surgery (corresponding approximately to
Examples
of procedures with a low risk of bleeding,
ve half-lives
of warfarin),
Dental Surgery Restorative Surgery and Extractions
Examples of xprocedures
with a low risk of bleeding,
o Anticoagulation can be continued with an INR of less than 3.0 and
x Dental Surgery appropriate

Restorative
Surgery
andmeasures
Extractions
topical
haemostatic
should be used. There is
no need to discontinue warfarin.
o Anticoagulation can be continued with an INR of less than 3.0 and

appropriate topical haemostatic measures should be used. There is
no need to discontinue warfarin.
x Minor Non-Invasive Surgery (e.g., dilation and curettage [D & C])
o Transient adjustment of the INR to below 1.5 for the perioperative
x Minor Non-Invasive Surgery (e.g., dilation and curettage [D & C])
period is required.
o xTransient
adjustment
of the(e.g.,
INR should
to below
1.5
for the
perioperative
Minor Non-Invasive
Surgery
dilation
and
curettage
& C])risk of
In cases
major
surgery,
consideration
be
given
to[D
the
x MajorofSurgery
of Anticoagulation
Required)
period(see
is(Interruption
required.
thromboembolism.
CHA2DS2Vasc scoring on page 29)
o Transient adjustment of the INR to below 1.5 for the perioperative
IIaC
IIaC
IIaC
IIaC
o In mostperiod
people
without mechanical prosthetic heart valves,
is required.
x Major Surgery (Interruption
of Anticoagulation Required)
anticoagulation can be safely discontinued temporarily, without the
xneed
Majorfor
Surgery
(Interruption
of Anticoagulation
Required)
heparin
cover. The
decision is made
on the basis of the
o In most people without mechanical prosthetic heart valves,
risk of thrombosis.
anticoagulation
be safely
discontinued
without
the
o In most can
people
without
mechanical temporarily,
prosthetic heart
valves,
need foranticoagulation
heparin cover.
decision
is madetemporarily,
on the basis
of the
canThe
be safely
discontinued
without
the
In patients with AF who
do
not
have
mechanical
prosthetic
heart
valves
or
those
need for heparin cover. The decision is made on the basis of the
risk of thrombosis.
who are not at high risk
risk offor
thrombo-embolism who are undergoing surgical or
thrombosis.
Keypoints
diagnostic procedures that carry a risk of bleeding, the interruption of OAC (with sub
In patients with AF who do not have mechanical prosthetic heart valves or those
patients with AF for
who
mechanical
prosthetic heart
valves
or those
therapeuticInanticoagulation
updotonot
48 have
h) should
be considered,
without
substituting
who
atarehigh
risk
for risk
thrombo-embolism
whowho
areare
undergoing
surgical or
IIaC
IIaCareasnot
who
notanticoagulation
at high
fortherapy.
thrombo-embolism
undergoing
heparin
bridging
(see Appendix
C.1.9
on pagesurgical
80). or
diagnostic diagnostic
procedures
that carry
risk of
bleeding,
the interruption
of of
OAC
procedures
thatacarry
a risk
of bleeding,
the interruption
OAC(with
(with sub
sub
therapeutictherapeutic
anticoagulation
for up to
should
be considered,
without
anticoagulation
for48
up h)
to 48
h) should
be considered,
withoutsubstituting
substituting
In patients
with
a
mechanical
prosthetic
heart
valve
or
AF
at
high
risk
for
as bridging
anticoagulation
therapy.
Appendix
C.1.9
page80).
80).
heparin asheparin
bridging
anticoagulation
therapy.
(see (see
Appendix
C.1.9
onon
page
thrombo-embolism who are undergoing surgical or diagnostic procedures,
bridging Inanticoagulation
with therapeutic
dosesvalve
of either
LMWH
or
patients
with a mechanical
prosthetic
high
risk for
for
InIIaC
patients with
a mechanical
prosthetic
heartheart
valve or or
AFAFatathigh
risk
IIaC
thrombo-embolism
whotheare
undergoing
surgical or
procedures,
unfractionated
heparin during
temporary
interruption
of diagnostic
OAC therapy
should
thrombo-embolism
who
are
undergoing
surgical
or
diagnostic
procedures,
bridging anticoagulation with therapeutic doses of either LMWH or
be considered.
bridging unfractionated
anticoagulation
of ofeither
LMWH
or
heparinwith
duringtherapeutic
the35
temporarydoses
interruption
OAC therapy
should
unfractionated
heparin during the temporary interruption of OAC therapy should
be considered.
Following surgical procedures, resumption of OAC therapy should be considered
need for heparin cover. The decision is made on the basis of the
riskAF
of who
thrombosis.
In patients with
do not have mechanical prosthetic heart valves or those
who are not at high risk for thrombo-embolism who are undergoing surgical or
In
patientsprocedures
with AF who
not ahave
mechanical
prosthetic
heartofvalves
or those
diagnostic
thatdocarry
risk of
bleeding, the
interruption
OAC (with
sub
who
are not
at high risk for
thrombo-embolism
who
are undergoing
surgical or
therapeutic
anticoagulation
for up
to 48 h) should be
considered,
without substituting
diagnostic
procedures
that
carry
a
risk
of
bleeding,
the
interruption
of
OAC
(with
heparin as bridging anticoagulation therapy. (see Appendix C.1.9 on page 80). sub
therapeutic anticoagulation for up to 48 h) should be considered, without substituting
heparin
as bridging
therapy. (see
C.1.9
In patients
with a anticoagulation
mechanical prosthetic
heartAppendix
valve or
AF on
at page
high 80).
risk for
thrombo-embolism who are undergoing surgical or diagnostic procedures,
In
patients anticoagulation
with a mechanical
heartdoses
valve or
at high
risk for
bridging
with prosthetic
therapeutic
of AF
either
LMWH
or
thrombo-embolism
whoduring
are the
undergoing
or diagnostic
procedures,
unfractionated heparin
temporarysurgical
interruption
of OAC therapy
should
bridging
anticoagulation with therapeutic doses of either LMWH or
be considered.
unfractionated heparin during the temporary interruption of OAC therapy should
be
considered.
Following
surgical procedures, resumption of OAC therapy should be considered
at the usual maintenance dose (without a loading dose) on the evening of (or
Following
surgicalafter)
procedures,
of OAC
therapy should
be considered
the next morning
surgery,resumption
assuming there
is adequate
haemostasis.
at the usual maintenance dose (without a loading dose) on the evening of (or
the nextsurgical
morningprocedures
after) surgery,
assuming
there is
haemostasis.
When
require
interruption
ofadequate
OAC therapy
for longer than
48h in high-risk patients, unfractionated heparin or subcutaneous LMWH may be
When
surgical
procedures
require
interruption
of
OAC
therapy
for longer than
considered.
48h in high-risk patients, unfractionated heparin or subcutaneous LMWH may be
considered.
6.4.2 ACUTE STROKE
IIaC
IIaC
IIaC
IIaC
IIaB
IIaB
IIaB
IIbC
IIbC
IIbC
6.4.2
STROKE
Keypoints
In allACUTE
patients
with AF who have had an acute stroke, any uncontrolled
IIaC
hypertension should be appropriately managed before antithrombotic therapy is

In
all .patients with AF who have had an acute stroke, any uncontrolled
started
hypertension should be appropriately managed before antithrombotic therapy is
started
. with AF and an acute stroke should have imaging done to exclude
Patients
IIaC
cerebral haemorrhage. In the presence of cerebral infarction, the decision on the
Patients
AF and anshould
acute be
stroke
should
have imaging
to exclude
IIaC
timing
of with
anticoagulation
weighed
between
the risk done
of haemorrhagic
IIaC
cerebral
haemorrhage.
In the
presence thromboembolism.
of cerebral infarction, the decision on the
transformation
and the risk
of recurrent
timing of anticoagulation should be weighed between the risk of haemorrhagic
transformation
and
the risk of
of recurrent
thromboembolism.
x In the
absence
haemorrhage,
anticoagulation may start 2 weeks
after stroke.
x
In
the
absence
of
haemorrhage,
anticoagulation
start 2 weeks
x In the presence of a large infarct, anticoagulation maymay
be delayed
after
after stroke.
IIaC
IIaC
2 weeks.
In the presence
of a large infarct,
anticoagulationshould
may be be
delayed
after
In thex presence
of haemorrhage,
anticoagulation
withheld
2 weeks.
until an appropriate
time.
x
In the presence of haemorrhage, anticoagulation should be withheld
until an appropriate time.

Patients with AFx and
a recent
TIAofshould
have imaging
done to
exclude
cerebral
In the
presence
a large infarct,
anticoagulation
may
be delayed
after
2 weeks.
haemorrhage.
Patients with AF and a recent TIA should have imaging done to exclude cerebral
IIaC
IIaC
x
IIaC
x In the presence of haemorrhage, anticoagulation should be withheld

haemorrhage.
until an of
appropriate
time.
In the absence
a haemorrhage,
anticoagulation should be started as
x possible.
In the absence of a haemorrhage, anticoagulation should be started as
soon as
Patients
with AF and a recent TIA should have imaging done to exclude cerebral
soon as possible.
haemorrhage.
In patients with AF who sustain ischaemic stroke or systemic embolism during

In
patients
with AF who
sustain ischaemic
systemic
embolism
during
treatment
with
usual
anticoagulation
withstroke
VKA or
(INR
2.03.0),
raising
x In intensity
the absence
of a haemorrhage,
anticoagulation
should be
startedthe
as
IIbC
IIb C
treatment with usual intensity anticoagulation with VKA (INR 2.03.0), raising the
soon as possible.to a maximum target INR of 3.03.5 may be
intensity of
the
anticoagulation
intensity of the anticoagulation to a maximum target INR of 3.03.5 may be
considered,
rather than
adding
an antiplatelet
agent.
considered,
rather
than adding
an antiplatelet
agent.
IIb C
In patients with AF who sustain ischaemic stroke or systemic embolism during
treatment with usual intensity anticoagulation with VKA (INR 2.03.0), raising the
6.4.3 Anticoagulant
and Antiplatelet
Therapy
UseUse
in Patients
With
6.4.3 Anticoagulant
and Antiplatelet
Therapy
in Patients
WithAtrial
Atrial
intensity of the anticoagulation to a maximum target INR of 3.03.5 may be
Fibrillation
Undergoing
Percutaneous
Coronary
Intervention
Fibrillation
Undergoing
Coronary
Intervention
considered,
ratherPercutaneous
than adding an antiplatelet
agent.
There
is of
a lack
of published
evidence
on what
is the
optimalmanagement
management
There is 6.4.3
a lack
published
onTherapy
what
is
optimal
Anticoagulant
andevidence
Antiplatelet
Usethe
in Patients
With Atrial
strategy in anticoagulated patients with nonvalvular atrial fibrillation (AF) who
Undergoing
Percutaneous
Coronary atrial
Intervention
strategy inFibrillation
anticoagulated
patients
with nonvalvular
fibrillation (AF) who
undergo percutaneous coronary intervention (PCI) and, hence, need antiplatelet
undergo percutaneous
coronary intervention (PCI) and, hence, need antiplatelet
therapy.
therapy. There is a lack of published evidence on what is the optimal management
strategyoninconsensus,
anticoagulated
patients strategy
with nonvalvular
fibrillation
who
Based
the post-PCI
should beatrial
tailored
to the (AF)
individual
undergo
percutaneous
intervention
hence,toneed
and
their
riskpost-PCI
of coronary
thromboembolism
and(PCI)
stent
thrombosis
weighed
against
Based on patient
consensus,
the
strategy
should
beand,
tailored
the antiplatelet
individual
therapy
their
risk. risk
of bleeding
while receiving triple
(see Table 13)
patient and
their
of thromboembolism
andtherapy
stent thrombosis
weighed against
their risk of
bleeding
while receiving
triple therapy
13) to the individual
Based
on consensus,
the post-PCI
strategy (see
shouldTable
be tailored
IIaC
Following elective PCI in patients with AF with stable coronary artery disease,
patient and their risk of thromboembolism and stent thrombosis weighed against
BMS should be considered, and drug-eluting stents avoided or strictly limited to
risk ofPCI
bleeding
while receiving
triple
therapy
(see
Table 13)artery disease,
Following their
elective
in patients
with AF
with
stable
coronary
Keypoints
those
clinical and/or
anatomical
situations
(e.g. long
lesions, small vessels,
BMS should
be considered,
drug-eluting
avoided
strictly limited
to
diabetes,
etc.), where and
a signicant
benetstents
is expected
whenor
compared
with BMS.
Following
elective
PCI
in
patients
with
AF
with
stable
coronary
artery disease,
those
IIaC clinical and/or anatomical situations (e.g. long lesions, small vessels,
IIaC
Following
elective
PCI, triple
therapy
(VKA, aspirin,
clopidogrel) with
should
be
diabetes, etc.),
where
a signicant
benet
is expected
when compared
BMS.
those clinical and/or anatomical situations (e.g. long lesions, small vessels,
IIaC
considered in the short term, followed by more long-term therapy (up to 1 year)
diabetes, etc.), where a signicant benet is expected when compared with BMS.
VKA plus
clopidogrel
75 mg daily
(or, alternatively,
aspirin 75100
mg daily).
Following with
elective
PCI,
triple therapy
(VKA,
aspirin, clopidogrel)
should
be
36 more
considered
in the short
term,
followed
by
long-term
(up to
1 year)
Following
elective
PCI,
triple therapy
(VKA,
aspirin,therapy
clopidogrel)
should
be
Following elective PCI, clopidogrel should be considered in combination with
IIaC
considered
in the short
term,
followed
by more long-term therapy
(up to daily).
1 year)
with VKA plus
daily
(or,
75100
VKA clopidogrel
plus aspirin 75
for mg
a minimum
of alternatively,
1 month after aspirin
implantation
of amg
BMS, but
patient and their risk of thromboembolism and stent thrombosis weighed against
IIaC
Following their
elective
in patients
with AF
with
stable
coronary
risk ofPCI
bleeding
while receiving
triple
therapy
(see
Table 13)artery disease,
Following
elective
PCI in patients
with AF
withlong
stablelesions,
coronarysmall
artery vessels,
disease,
those
clinical
and/or
anatomical
situations
(e.g.
IIaC
considered, benet
and drug-eluting
stents
avoided
or strictly
limited
to
diabetes, BMS
etc.),should
wherebe
a signicant
is expected
when
compared
with
BMS.
those clinical and/or anatomical situations (e.g. long lesions, small vessels,
IIaC
where a signicant benet is expected when compared with BMS.

Following diabetes,
electiveetc.),
PCI,
triple therapy (VKA, aspirin, clopidogrel) should be
considered
in
the
short
term,
by more
long-term
(up to
1 year)
Following elective
PCI,followed
triple therapy
(VKA,
aspirin,therapy
clopidogrel)
should
be
IIaC
IIaCVKA considered
with
plus clopidogrel
75 mg
daily
(or, alternatively,
aspirintherapy
75100
in the short
term,
followed
by more long-term
(upmg
to 1daily).
year)
with VKA plus clopidogrel 75 mg daily (or, alternatively, aspirin 75100 mg daily).
IIaC
Following elective PCI, clopidogrel should be considered in combination with

elective
PCI, clopidogrel
shouldafter
be considered
in combination
VKA
aspirin for
a minimum
of 1 month
implantation
of a BMS, with
but
IIaC
IIaC plusFollowing
VKA
plus aspirin forstent
a minimum
of 3
1 months
month after
of a BMS,stent
but
longer with
a drug-eluting
(at least
for implantation
a sirolimus-eluting
longer with a drug-eluting stent (at least 3 months for a sirolimus-eluting stent
and at least 6 months for a paclitaxel-eluting stent); following which VKA and
and at least 6 months for a paclitaxel-eluting stent); following which VKA and
clopidogrel
75 mg daily
(or,
alternatively,
aspirin
75100
mgmg
daily).
clopidogrel
75 mg
daily
(or, alternatively,
aspirin
75100
daily).
6.4.4 NON-ST
ELEVATION
MYOCARDIAL
INFARCTION
6.4.4 NON-ST
ELEVATION
MYOCARDIAL
INFARCTION
patients
with non-ST
elevation
myocardial
infarction,
dual
antiplatelet therapy
therapy
In patientsIn with
non-ST
elevation
myocardial
infarction,
dual
antiplatelet
with aspirin plus clopidogrel is recommended, but in AF patients at moderate to
high risk of stroke, OAC should also be given.
In the acute setting, patients are often given aspirin, clopidogrel, UFH, or LMWH
(e.g. enoxaparin) or bivalirudin and/or a glycoprotein IIb/IIIa inhibitor (GPI). Drugeluting stents should be limited to clinical situations, as described above (see
Table 13). An uninterrupted strategy of OAC is preferred, and radial access
should be used as the rst choice.
For medium to long-term management, triple therapy (VKA, aspirin, and
clopidogrel) should be used in the initial period (3 6 months), or for longer in
selected patients at low bleeding risk. In patients with a high risk of
cardiovascular thrombotic complications [e.g. high Global Registry of Acute
Coronary Events (GRACE) or TIMI risk score], long-term therapy with VKA may
be combined with clopidogrel 75 mg daily (or, alternatively, aspirin 75 100 mg
daily).
Table 13: Antithrombotic
strategies following coronary artery stenting in patients with AF at moderate to high
<<Table
13>>
thrombo-embolic risk (in whom oral anticoagulation therapy is required)
IIaC
Haemorrhagic risk
Clinical
Stent implanted
Anticoagulation regimen
Following
an ACS with or
without PCI
in patients with AF,
triple therapy (VKA,
setting
aspirin,
clopidogrel)
term
Low or intermediate
(e.g should
Elective be considered
Bare-metal in the short
1 month:
triple(36
therapymonths),
of VKA (INRor
HAS-BLED
0-2) patients at low bleeding risk, followed
2.0-2.5) +
75-100mg/day
longer
in score
selected
byaspirin
long-term
therapy
+clopidogrel 75 mg/day
with VKA plus clopidogrel 75 mg daily (or, alternatively,
aspirin 75100 mg daily).
Lifelong: VKA (INR 2.0-3.0) alone
Elective
IIaC
IIbC
Drug-eluting
VKA (INR 2.0-2.5) + clopidogrel

75/dayb
When VKA is given in combination with clopidogrel or

low-dose
aspirin, careful
(or aspirin
100m/day)
regulation of the anticoagulation dose intensity may be
considered,
with alone
an INR
Lifelong:
VKA (INR 2.0-3.0)
ACS
Bare-metal/drug6
months:
triple
therapy
of VKA (INR
range of 2.02.5.
eluting
IIbC
2.0-2.5) + aspirin 75-100mg/day

Following revascularization surgery in patients with

AF,
plus a single
Up to
12th VKA
month: combination
of
VKA (INR but
2.0-2.5)
antiplatelet drug may be considered in the initial 12 months,
this+ clopidogrel
strategy has
75/dayb
not been evaluated thoroughly and is associated with (or
anaspirin
increased
risk of
100m/day)
bleeding.
High
(e.g, HAS-BLED score
IIbC
3 (-olimusa group) to 6 (paclitaxel)
months: triple therapy

of VKA (INR
In anticoagulated patients at very high risk of thrombo-embolism,
uninterrupted
2.0-2.5) + aspirin 75-100mg/day
therapy with VKA as the preferred strategy and radial
access used as the rst
th
choice even during therapeutic anticoagulation (INR 23).
Up to 12 month: combination of
Elective
Bare-metalc
2-4 weeks: triple therapy of VKA

(INR 2.0-2.5) + aspirin 75-
In>3)
patients with stable vascular disease (e.g. >1 year, 100mg/day
with no acute
events),
VKA
+clopidogrel
75 mg/day
VKA (INR
2.0-3.0) alone
monotherapy may be considered, and concomitant Lifelong:
antiplatelet
therapy
should
ACS
4 weeks: triple therapy
not be prescribed in the
absence of Bare-metalc
a subsequent cardiovascular
event.of VKA (INR
2.0-2.5) + aspirin 75-100mg/day
(or aspirin 100m/day)
ACS = acute coronary syndrome; AF = atrial fibrillation;

37 INR = international normalized ratio; VKA = vitamin
K antagonist.
Gastric protection with a proton pump inhibitor (PPI) should be considered where necessary.
Lifelong:
(INR 2.0-3.0)
alone to
with aspirin plus clopidogrel is recommended, but
in AFVKA
patients
at moderate
High
ElectiveOAC should
Bare-metalc
high risk of stroke,
also be given.
(e.g, HAS-BLED score
>3)
2-4 weeks: triple therapy of VKA

(INR 2.0-2.5) + aspirin 75100mg/day +clopidogrel 75 mg/day
In the acute setting, patients are often given aspirin,
clopidogrel,
UFH, or
LMWH
Lifelong:
VKA (INR 2.0-3.0)
alone
(e.g. enoxaparin)
and/or a glycoprotein
IIb/IIIa
DrugACS or bivalirudin
Bare-metalc
4 weeks:
tripleinhibitor
therapy of(GPI).
VKA (INR
eluting stents should be limited to clinical situations,
described
above (see
2.0-2.5) as
+ aspirin
75-100mg/day
+clopidogrel
75
mg/day
Table 13). An uninterrupted strategy of OAC is preferred, and radial access
(or aspirin 100m/day)
should be used as the rst choice.
For medium to long-term management, triple therapy (VKA, aspirin, and
ACS = acute coronary syndrome; AF = atrial fibrillation; INR = international normalized ratio; VKA = vitamin
clopidogrel) should be used in the initial period (3 6 months), or for longer in
K antagonist.
selected
patients
low (PPI)
bleeding
risk.
In patients
with a high risk of
Gastric protection
with a proton
pumpatinhibitor
should be
considered
where necessary.
a
cardiovascular
thrombotic complications [e.g. high Global Registry of Acute
Sirolimus, everolimus,
and tacrolimus.
b
CombinationCoronary
of VKA (INR
2.03.0)+aspirin
mg/day
PPI, long-term
if indicated)therapy
may be considered
an
Events
(GRACE)100
or TIMI
risk(with
score],
with VKA as
may
alternative. be combined with clopidogrel 75 mg daily (or, alternatively, aspirin 75 100 mg
c
Drug-eluting stents should be avoided as far as possible, but, if used, consideration of more prolonged (36
daily).
months) triple antithrombotic therapy is necessary.
54
Adapted from Lip et al.
<<Table 13>>
Keypoints
IIaC
IIaC
Following an ACS with or without PCI in patients with AF, triple therapy (VKA,
aspirin, clopidogrel) should be considered in the short term (36 months), or
longer in selected patients at low bleeding risk, followed by long-term therapy
with VKA plus clopidogrel 75 mg daily (or, alternatively, aspirin 75100 mg daily).
IIaC
IIaC
In anticoagulated patients at very high risk of thrombo-embolism, uninterrupted

therapy with VKA as the preferred strategy and radial access used as the rst
choice even during therapeutic anticoagulation (INR 23).
IIbC
IIbC
When VKA is given in combination with clopidogrel or low-dose aspirin, careful

regulation of the anticoagulation dose intensity may be considered, with an INR
range of 2.02.5.
IIbC
IIbC
Following revascularization surgery in patients with AF, VKA plus a single

antiplatelet drug may be considered in the initial 12 months, but this strategy has
not been evaluated thoroughly and is associated with an increased risk of
bleeding.
IIbC
IIbC
In patients with stable vascular disease (e.g. >1 year, with no acute events), VKA
monotherapy may be considered, and concomitant antiplatelet therapy should
not be prescribed in the absence of a subsequent cardiovascular event.
6.4.5
6.4.5 CARDIOVERSION
CARDIOVERSION
Conversion
transient mechanical
mechanical dysfunction
dysfunction of
of
Conversion of
of AF
AF to
to 70sinus
sinus rhythm
rhythm results
results in
in transient
70
the
and
LAA
("stunning"),
which can
the LA
LA 6.4.5
and CARDIOVERSION
LAA
("stunning"),
can occur
occur after
after spontaneous,
spontaneous,
48,71
71-73 which
48,71 or electrical71-73 conversion of AF. Thrombus may form
pharmacological,
of AF.mechanical
Thrombusdysfunction
may form
pharmacological,
transient
of
Conversionofofor
AFelectrical
to sinus
rhythmconversion
results in after
during
and
the return
of mechanical
during the
thetheperiod
period
of stunning
stunning
and is
is expelled
expelled
return
mechanical
LA and
LAA70 ("stunning"),
which after
can the
occur
afterof spontaneous,
of
thromboembolic
events
during
the
first
10
d
function,
explaining
the
clustering
48,71
71-73
of thromboembolic
the first
d
function, explaining
the clustering
or electrical
conversionevents
of AF. during
Thrombus
may 10
form
pharmacological,
74,75
after
mechanical
may
delayed,
during the 74,75
periodRecovery
of stunningof
is expelled function
after the
return
of mechanical
after cardioversion.
cardioversion.
Recovery
ofand
mechanical
function
may be
be
delayed,
76,46,87
76,46,87
depending
partially
on
the
duration
of
AF
before
conversion.
thromboembolic
events during the first 10 d
the clustering
dependingfunction,
partiallyexplaining
on the duration
of AFofbefore
conversion.
after cardioversion.74,75 Recovery of mechanical function may be delayed,
77,78
76,46,87
partially on the
duration
of AF before
The
thromboembolism
after
cardioversion
is
between
1% and
and 5%
5%77,78 and
and
The risk
risk of
ofdepending
thromboembolism
after
cardioversion
is conversion.
between 1%
is reduced
reduced when
anticoagulation
(INR
2.0
to
3.0)
is
given
for
4
wk
before
and
is
when
anticoagulation
(INR
2.0
to
3.0)
is
given
for
4
wk
before
77,78and
79,80
1%
and
5%
and
The
risk
of
thromboembolism
after
cardioversion
is
between
(see Figure
Figure 9).
9).
after conversion
conversion79,80 (see
after
is reduced when anticoagulation (INR 2.0 to 3.0) is given for 4 wk before and
79,80
(see Figure 9).

after conversion
Keypoints
For
patients
For
patients with
with AF
AF or
or AFL
AFL of
of 48-h
48-h duration
duration or
or longer,
longer, or
or when
when the
the duration
duration of
of
AF
or
AFL
is
unknown,
anticoagulation
(INR
2.0
is
recommended
for
For
patients
with
AF
or AFL of 48-h
duration
or 3.0)
longer,
when the duration
of
AF
or AFL is unknown, anticoagulation
(INR
2.0 to
to
3.0)
is or
recommended
for at
at
IB
IB
least
4
after
of
AF orprior
AFL to
is and
unknown,
anticoagulation
(INR 2.0 toregardless
3.0) is recommended
for at
least 4
4 weeks
weeks
prior
to
and
4 weeks
weeks
after cardioversion,
cardioversion,
regardless
of the
the method
method
64
least 4sinus
weeksrhythm.
prior to 64
and 4 weeks after cardioversion, regardless of the method
used
used to
to restore
restore
sinus
rhythm.
used to restore sinus rhythm.64
For
with AF
requiring
immediate/emergency
cardioversion
because of
For patients
patients
AF with
requiring
immediate/emergency
cardioversion
For with
patients
AF requiring
immediate/emergency
cardioversionbecause
because of
of
haemodynamic
instability,
heparin
(i.v.
bolus
followed
by
infusion,
or weightICIC
haemodynamic
instability,
heparinheparin
(i.v. UFH
UFH
bolusbolus
followed
by by
infusion,
haemodynamic
instability,
(i.v. UFH
followed
infusion,ororweightweightadjusted
therapeutic
dose
LMWH)
is
recommended.
adjusted therapeutic
dose LMWH)
is recommended.
adjusted therapeutic
dose LMWH)
is recommended.
After
cardioversion
in
with
AF
of
48
After immediate/emergency
cardioversion
in patients
hourduration
duration
After immediate/emergency
immediate/emergency
cardioversion
in patients
patients
withwith
AFAF
of of
4848hour
hour
duration
the duration
is unknown,
therapy
recommended
orI IB
longer, or
or
when
the
duration
of
is
unknown,
OAC
therapy
is
recommended
B
or
longer,
orlonger,
when or
thewhen
duration
of AF
AF of
is AF
unknown,
OACOAC
therapy
is is
recommended
6464
for
at
least
4
weeks,
similar
to
patients
undergoing
elective
cardioversion.
64
for at
at least
least 4
4 weeks,
weeks, similar
similar to
to patients
patients undergoing
undergoing elective
elective cardioversion.
cardioversion.
for
AF duration
that38is clearly
<48
h and no
thrombo-embolic risk
risk
Forwith
patients
AF with
duration
that is
<48
h
For
patients
with i.v.
AF
duration
is clearly
clearly
<48 therapeutic
h and
and no
no thrombo-embolic
thrombo-embolic
For
factors,
heparin orthat
weightadjusted
dose LMWH mayrisk
be
IIbCpatients
factors,
i.v. heparin or weightadjusted therapeutic dose LMWH may be
IC
For patients with AF requiring immediate/emergency cardioversion because of

haemodynamic instability, heparin (i.v. UFH bolus followed by infusion, or weightadjusted therapeutic dose LMWH) is recommended.
IB
After immediate/emergency cardioversion in patients with AF of 48 hour duration

or longer, or when the duration of AF is unknown, OAC therapy is recommended
for at least 4 weeks, similar to patients undergoing elective cardioversion. 64
IIbC
IIbC
For patients with AF duration that is clearly <48 h and no thrombo-embolic risk
factors, i.v. heparin or weightadjusted therapeutic dose LMWH may be
considered peri-cardioversion, without the need for post-cardioversion oral
anticoagulation.
It is important to stress that in following cardioversion of all patients at high risk of
AF recurrence or with stroke risk factors, consideration should be given towards
long-term anticoagulation, as thromboembolism may occur during asymptomatic
recurrence of AF.
IIB
B
IIB
B
For patients with AF <48 h and at high risk of stroke, i.v. heparin or weightadjusted therapeutic dose LMWH is recommended peri-cardioversion, followed
by OAC therapy with a VKA (INR 2.03.0) long term.49,55,64
In patients at high risk of stroke, OAC therapy with a VKA (INR 2.03.0) is
recommended to be continued long-term.49,55,64
<<Figure 9>>
Figure 9: Cardioversion of haemodynamically stable AF, the role of TOE-guided cardioversion, and
subsequent anticoagulation strategy. AF = atrial fibrillation; DCC = direct current cardioversion; LA = left
atrium; LAA = left atrial appendage; OAC = oral anticoagulant; SR = sinus rhythm; TOE = transoesophageal
echocardiography.
39
As an alternative to anticoagulation prior to cardioversion of AF or AFL, it is

reasonable to perform TOE in search of thrombus.13
x For As
patients
with noto identifiable
thrombus,
cardioversion
is or
reasonable
an alternative
anticoagulation
prior to cardioversion
of AF
AFL, it is
immediately
anticoagulation.
reasonableafter
to perform
TOE in search of thrombus.13
IBIB
x For continuation
patients with no
thrombus, cardioversion
x Thereafter,
of identifiable
(INR 2.0 istoreasonable
3.0) is
IIaB
IIaB
immediately
after
reasonable
for at least
4 anticoagulation.
weeks, as for elective cardioversion.
x Thereafter, continuation of oral anticoagulation (INR 2.0 to 3.0) is
IIaB
x For patients in whom thrombus is identified, oral anticoagulation (INR 2.0 to
IIaB
reasonable for at least 4 weeks, as for elective cardioversion.
IIaB
IIaB
3.0) is reasonable for at least 4 weeks before and 4 weeks after

restoration
sinusinrhythm,
and longer
anticoagulation
may be appropriate
x For of
patients
whom thrombus
is identified,
(INR 2.0 to
after apparently
successful
because
risk after
of
3.0) is reasonable
for atcardioversion,
least 4 weeks before
and the
4 weeks
thromboembolism
remains
such cases. may be appropriate
restorationoften
of sinus
rhythm,elevated
and longerinanticoagulation
after
apparently
successful
cardioversion,
because
the
risk
of
thromboembolism
often remains
elevated
in suchthrombus
cases.
For patients undergoing
a TOE-guided
strategy
in whom
is identied,
VKA (INR 2.03.0) is recommended for at least 4 weeks, followed by a repeat
For
patients
undergoing
a
TOE-guided
strategy
in
whom
thrombus
is identied,
ICIC to ensure thrombus resolution.
TOE
VKA (INR 2.03.0) is recommended for at least 4 weeks, followed by a repeat
TOE to ensure thrombus resolution.
If thrombus resolution is evident on repeat TOE, cardioversion should be

performed,If and
OAC should
be isconsidered
4 weeks
lifelong (if risk
factors
thrombus
resolution
evident onfor
repeat
TOE,orcardioversion
should
be
IIaC
IIaC
performed, and OAC should be considered for 4 weeks or lifelong (if risk factors
are
present).
are present).
If thrombus remains on repeat TOE, an alternative strategy (e.g. rate control)

If thrombus remains on repeat TOE, an alternative strategy (e.g. rate control)
IIbCbe considered.
may
IIbC
may be considered.
be useful
allow
cardioversion
of patients
This strategy
may be to
useful
to early
allow early
cardioversion
of patientswith
withAF
AF !! 48
48
Thismay
strategy
hours or
where a minimal
of anticoagulation
is preferred.
hours or where
a minimal
period period
of anticoagulation
is preferred.
6.5 NON-PHARMACOLOGICAL
METHODS
TO PREVENT
STROKE
6.5 NON-PHARMACOLOGICAL
METHODS
TO PREVENT
STROKE
The left atrial appendage (LAA) is considered the main site of atrial
The left thrombogenesis

atrial appendage
(LAA)occlusion
is considered
the orice
main may
site reduce
of atrial
and thus,
of the LAA
the
thrombogenesis
and ofthus,
occlusion
of the
LAA with
orice
development
atrial thrombi
and stroke
in patients
AF may reduce the
development of atrial thrombi and stroke in patients with AF
The PROTECT AF trial81 randomized 707 eligible patients to percutaneous
81 using a WATCHMAN device and subsequent discontinuation

closure of
LAA
randomized 707 eligible patients to percutaneous
The PROTECT
AFthetrial
warfarin
(intervention,
n = 463), ordevice
to VKA and
treatment
(INR range
2 3; control,
closure ofofthe
LAA using
a WATCHMAN
subsequent
discontinuation
n = 244). The primary efficacy event rate (a composite endpoint of stroke,
of warfarin (intervention, n = 463), or to VKA treatment (INR range 2 3; control,
cardiovascular death, and systemic embolism) of the WATCHMAN device was
n = 244).considered
The primary
efficacy
event
rateThere
(a composite
of stroke,
non-inferior
to that
of VKA.
was a higherendpoint
rate of adverse
safety
cardiovascular
systemicgroup
embolism)
thecontrol
WATCHMAN
device
was
eventsdeath,
in theand
intervention
than inofthe
group, due
mainly
to
consideredperiprocedural
non-inferior complications.
to that of VKA. There was a higher rate of adverse safety
events in the intervention group than in the control group, due mainly to
periprocedural complications.
6.6 RISK OF LONG-TERM ANTICOACULATION

6.6.1. ASSESSMENT OF RISK OF BLEEDING
An assessment of bleeding risk should be part of the clinical assessment of
patients before starting anticoagulation therapy.
In order to provide adequate thromboprophylaxis with minimal risk of bleeding,
current clinical practice aims for a target INR of between 2.0 and 3.0; INRs of
more than 3.0 are associated with increases in bleeding and INRs of less than
2.0 are associated with increases in stroke risk.
The annual risks of intracranial haemorrhage increased from 0.1% in control to
0.3% in VKA groups, which represents 40
an excess of two intracranial bleeds per
annum per 1,000 patients treated.
6.6 RISK OF LONG-TERM ANTICOACULATION

6.6.1. ASSESSMENT OF RISK OF BLEEDING
An assessment of bleeding risk should be part of the clinical assessment of
patients before starting anticoagulation therapy.
In order to provide adequate thromboprophylaxis with minimal risk of bleeding,
current clinical practice aims for a target INR of between 2.0 and 3.0; INRs of
more than 3.0 are associated with increases in bleeding and INRs of less than
2.0 are associated with increases in stroke risk.
The annual risks of intracranial haemorrhage increased from 0.1% in control to
0.3% in VKA groups, which represents an excess of two intracranial bleeds per
annum per 1,000 patients treated.
Even low-dose aspirin increases the risk of major haemorrhage by two-fold,
especially in the setting of uncontrolled hypertension.
Controlling and monitoring of hypertension and other associated co morbidities is
extremely important in minimizing the risk of bleeding in patients on prophylactic
OAC.
The fear of falls may be overstated, as a patient may need to fall 300 times per
year for the risk of intracranial haemorrhage to outweigh the benet of OAC in
stroke prevention.
While these factors are often cited as reasons for non-prescription of VKA in the
elderly, the absolute benefit is likely to be greatest in this same group in view of
their high risk.68
6.6.2 RISK SCORE FOR BLEEDING
The bleeding risk score HAS-BLED was formulated by incorporating risk factors
from a derivation cohort of a large population database of the prospective Euro
Heart Survey on AF.82 The clinical characteristic comprising the HAS-BLED
bleeding risk score is shown in Table 14.
It is reasonable to use the HAS-BLED score to assess bleeding risk in AF
patients, whereby a score of 3 indicates high risk, and some caution and
regular review of the patient is needed following the initiation of antithrombotic
therapy, whether with VKA or aspirin.
A schema such as HAS-BLED is a user-friendly method of predicting bleeding
risk and is easy to remember.
41
Table 14 : Clinical characteristics comprising the HAS-BLED bleeding risk score
Table 14 : Clinical characteristics comprising the HAS-BLED bleeding risk score
Letter
Clinical characteristica
Points awarded
1
Hypertension
Abnormal renal and liver

function (1 point each)
Stroke
Bleeding
Labile INRS
Elderly (e.g. age >65 years)
Drugs or alcohol (1 point each)
1 or 2
1 or 2
Maximum 9 points
Hypertension is defined as systolic blood pressure .160 mmHg. Abnormal kidney function is defined
as the presence of chronic dialysis or renal transplantation or serum creatinine 200 mmol/L. Abnormal
liver function is defined as chronic hepatic disease (e.g. cirrhosis) or biochemical evidence of significant
hepatic derangement (e.g. bilirubin .2 x upper limit of normal, in association with aspartate
aminotransferase/alanine
aminotransferase/alkaline
a
Hypertension
blood
pressure
.160 refers
mmHg.toAbnormal
function
is defined
phosphatase
.3 isx defined
upper as
limitsystolic
normal,
etc.).
Bleeding
previous kidney
bleeding
history
and/or
as the presence
chronic e.g.
dialysis
or renal
transplantation
or etc.
serum
creatinine
Abnormal
predisposition
to of
bleeding,
bleeding
diathesis,
anaemia,
Labile
INRs200
refersmmol/L.
to unstable/high
liver function
defined
as chronic range
hepatic(e.g.<60%).
disease (e.g.
cirrhosis) or use
biochemical
of significant
INRs
or poor is
time
in therapeutic
Drugs/alcohol
refers toevidence
concomitant
use of
hepaticsuch
derangement
(e.g.
bilirubin
.2 x upper
limit of normal,
in orassociation
with etc.
aspartate
drugs,
as antiplatelet
agents,
non-steroidal
anti-inflammatory
drugs,
alcohol abuse,
INR =
aminotransferase/alanine
aminotransferase/alkaline
international
normalized ratio.
82
phosphatase
.3 x upper
Adapted
from Pisters
et al. limit normal, etc.). Bleeding refers to previous bleeding history and/or
predisposition to bleeding, e.g. bleeding diathesis, anaemia, etc. Labile INRs refers to unstable/high
INRs or poor time in therapeutic range (e.g.<60%). Drugs/alcohol use refers to concomitant use of
drugs, such<<Table
as antiplatelet
14>>agents, non-steroidal anti-inflammatory drugs, or alcohol abuse, etc. INR =
Keypoints
international normalized ratio.
82
Adapted from Pisters et al.
IIaA
IIaA
Assessment of the risk of bleeding should be considered when prescribing

antithrombotic therapy (whether with VKA or aspirin), and the bleeding risk with
aspirin should be considered as being similar to VKA, especially in the
elderly.68,82,83
IIaB
IIaB
The HAS-BLED score [hypertension, abnormal renal/liver function, stroke,

bleeding history or predisposition, labile INR, elderly (>65), drugs/alcohol
concomitantly] should be considered as a calculation to assess bleeding risk,
whereby a score of 3 indicates high risk and some caution and regular review
is needed, following the initiation of antithrombotic therapy, whether with OAC or
aspirin.82
7 MANAGEMENT LONGTERM RATE CONTROL

7.1 PHARMACOLOGICAL RATE CONTROL
Criteria for rate control vary with patient age but usually involve achieving
ventricular rates
x 60 - 80 beats per minute at rest and
x 90 115 beats per minute during moderate exercise.23
However, maintaining lenient control of heart rate (a resting rate of less than 100
beats per minute) is easier to achieve and is comparable to strict control (a
resting heart rate of 80 beats per minute
and a heart rate during moderate
42
exercise of less than 110 beats per minute) on long-term composite outcomes.84
7.1 PHARMACOLOGICAL RATE CONTROL

ventricular rates
x 60 - 80 beats per minute at rest and
x 90 115 beats per minute during moderate exercise.23
However, maintaining lenient control of heart rate (a resting rate of less than 100
beats per minute) is easier to achieve and is comparable to strict control (a
resting heart rate of 80 beats per minute and a heart rate during moderate
exercise of less than 110 beats per minute) on long-term composite outcomes.84
For patients without severe symptoms due to high ventricular rate, a lenient rate
control therapy approach is reasonable (See Figure 10).
<<Figure 10>>
Drugs commonly used are -blockers, non-dihydropyridine calcium channel

antagonists, and digitalis. Acute treatment is described in Section 5.1.1.
7 MANAGEMENT
LONGTERM
RATE CONTROL
Combinations
of drugs
may be necessary.
Dronedarone may also effectively
reduce heart rate during AF recurrences. Amiodarone may be suitable for some
7.1
PHARMACOLOGICAL
RATErate
CONTROL
patients
with otherwise refractory
control. The combination of a
-blocker and digitalis may be benecial in patients with heart failure.
ventricular
rates
When a strict
rate control policy is adopted (resting heart rate < 80 bpm and a
x 60rate
- 80 of
beats
perbpm
minute
at rest
and exercise) a 24 h Holter monitor
target heart
<110
during
moderate
115 beats
per minute
during
moderate exercise.23
should xbe 90
performed
to assess
pauses
and bradycardia.
However,
maintaining
lenient control
of heart rate
(a restingagent,
rate oforless
than 100
Selection of
the most effective
and appropriate
rate-control
combination
beats
per minute)
is easier
to achieve
and treatments
is comparable
to strict
control (a
of agents,
is vital. Table
15 lists
rate-control
in order
of preference,
resting
heart
rate ofother
80 beats
per minute
andbea present.
heart rate
during
taking into
account
conditions
that may
Figure
11, moderate
page 47
84
exercise
than 110
permake
minute)
long-term
provides of
anless
algorithm
on beats
how to
theondrug
choicecomposite
and Tableoutcomes.
16 list the
For patients
without
symptoms
drugs
and their
dosessevere
for rate
control. due to high ventricular rate, a lenient rate
control therapy approach is reasonable (See Figure 10).
<<Table
15>> level of heart rate control.
Figure 10:Optimal
<<Figure 10>>
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European
<<Table 16>>
heart Journal 2010; doi:10.1093/eurheartj/ehq278)
Drugs commonly used are -blockers, non-dihydropyridine calcium channel

antagonists, and digitalis. Acute treatment is described in Section 5.1.1.
Combinations of drugs may be necessary. Dronedarone may also effectively
reduce heart rate during AF recurrences. Amiodarone may be suitable for some
patients with otherwise refractory rate control. The combination of a
-blocker and digitalis may be benecial in patients with heart failure.
When a strict rate control policy is adopted (resting heart rate < 80 bpm and a
target heart rate of <110 bpm during moderate exercise) a 24 h Holter monitor
should be performed to assess pauses and bradycardia.
Selection of the most effective and appropriate rate-control agent, or combination
of agents, is vital. Table 15 lists rate-control treatments in order of preference,
taking into account other conditions that may be present. Figure 11, page 47
provides an algorithm on how to make the drug choice and Table 16 list the
drugs and their doses for rate control.
<<Table 15>>
<<Table 16>>
43
Table 15: Choice of a rate-control agent

Co morbidity
First-line
No heart disease
Beta-blockers*
OR
Non-dihydropyridine
Calcium channel
blockers
Hypertension
Beta-blockers*
OR
Non-dihydropyridine
Calcium channel
blockers
Beta-blockers*
Ischaemic heart
disease
Congestive heart
failure
Second-line
Digoxin
Digoxin in overt heart

failure
Carvedilol or bisoprolol
or metoprolol
in stable heart failure
Chronic obstructive
pulmonary disease
Less effective or
desirable
Digoxin
(can be rst-line in
people unlikely to be
active)
Non-dihydropyridine
Calcium channel
blockers
First line agent plus

Non-dihydropyridine
Calcium-channel
blockers
OR
Digoxin
Ablation + pacing
Beta-blockers*
(excluding carvedilol,
bisoprolol
and metoprolol)
OR
Diltiazem
Amiodarone
First line agent plus

beta-blockers
(if there is no
reversible
bronchospasm.
Digoxin
Ablation and pacing

should be considered
* excluding sotalol
diltiazem or verapamil
as monotherapy (can be used in combination with other rate-control agents)
Adapted from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal
44
Table 16: Oral pharmacological agents for rate control in people with atrial fibrillation/atrial flutter
Drug
Oral
loading
dose
Onset
of action
Commonly used
oral maintenance
doses
Beta-blockers
Atenolol
N/A
2 to 3 hr
25 to 50 mg
Carvedilol
N/A
60 to 90 min
6.25 to 25 mg bd
Metoprolol
N/A
4 to 6 hr
23.75 to 200 mg/day *
Nadolol
N/A
3 to 4 hr
20 to 80 mg/day
Propanolol
N/A
Adverse effects
Hypotension,
heart block,
bradycardia,
asthma, heart failure
In people with
heart failure,
lower doses may
be advisable
(negative inotropic
effect)
In people with
heart failure,
lower doses may
be advisable
In people with
heart failure,
lower doses may
be advisable
(negative
inotropic effect)
60 to 90 min
80 to 240 mg/day
Calcium channel blockers

Diltiazem
N/A
1 to 4 hr
120 to 360 mg/day
Hypotension,
heart block,
heart failure
Verapamil
1 to 2 hr
120 to 360 mg/day
Hypotension,
heart block,
heart failure,
digoxin
interaction
N/A
Comments
Other
Digoxin
0.5 to 1.0
mg
2 hr
0.0625 to 0.375
mg/day
Digoxin toxicity,
heart block,
bradycardia
Amiodarone
400 to 800
mg/day
for 1 week
1 to 3 wk
200 mg/day
Photosensitivity
and other skin
reactions,
pulmonary
toxicity,
polyneuropathy,
gastrointestinal
upset,
bradycardia,
hepatic toxicity,
thyroid
dysfunction,
torsades de
pointes (rare)
First-line therapy
only for people
unlikely to be active
(eg, older people or
infirm) and for
people with heart
failure.
Less effective in
hyperadrenergic
states
Although there
is fairly good
evidence of
efficacy, this is
an agent of last
resort in this
indication, due
to its long-term
toxicity
N/A = Not applicable

Adapted from: Fuster V, Ryden LE, Asinger RW, et al.134
Keypoints
IB
IB
IC
IC
ICIC
IIbB
Rate control using pharmacological agents (-blockers, non-dihydropyridine

calcium channel antagonists, digitalis, or a combination thereof) is recommended
in patients with paroxysmal, persistent, or permanent AF. The choice of
medication should be individualized and the dose modulated to avoid
bradycardia.34
In patients who experience symptoms related to AF during activity, the adequacy
of heart rate control should be assessed during exercise, adjusting
pharmacological treatment as necessary to keep the rate in the physiological
range.
In pre-excitation AF, or in patients with a history of AF, preferred drugs for rate
control are propafenone or amiodarone
It is reasonable to initiate treatment
45 with a lenient rate control protocol aimed at a
resting heart rate <110 bpm.84
IC
In patients who experience symptoms related to AF during activity, the adequacy

of heart rate control should be assessed during exercise, adjusting
pharmacological treatment as necessary to keep the rate in the physiological
range.
IC
In pre-excitation AF, or in patients with a history of AF, preferred drugs for rate
control are propafenone or amiodarone
IIbB
IIbB
It is reasonable to initiate treatment with a lenient rate control protocol aimed at a

resting heart rate <110 bpm.84
IIbB
IIbB
It is reasonable to adopt a stricter rate control strategy when symptoms persist or

tachycardiomyopathy occurs, despite lenient rate control: resting heart rate <80
bpm and heart rate during moderate exercise <110 bpm. After achieving the strict
heart rate target, a 24 h Holter monitor is recommended to assess safety.84
IIa
C
IIaC
Digoxin is indicated in patients with heart failure and LV dysfunction, and in

sedentary (inactive) patients.
IIbC
IIb
C
Rate control may be achieved by administration of oral amiodarone when other

measures are unsuccessful or contraindicated.
IIIB
III
B
Digitalis should not be used as the sole agent to control the rate of ventricular
response in patients with paroxysmal AF.88
IB
IB
Intravenous administration of amiodarone is recommended to control the heart

rate in patients with AF and HF who do not have an accessory pathway.
IIaC
IIaC
Intravenous amiodarone can be useful to control the heart rate in patients with
AF when other measures are unsuccessful or contraindicated. 35
7.1.2 Combination therapy

Combination of drugs may be required to control heart rate. Care should be
taken to avoid
severe bradycardia. The combination of digoxin and -blocker
7.1.2 Combination therapy
appears more effective than the combination of digoxin with a CCB.89
Combination of drugs may be required to control heart rate. Care should be
taken of
to avoid
severe
The combination
of digoxin
and -blocker
A combination
digoxin
andbradycardia.
either a -blocker,
diltiazem,
or verapamil
is
Keypoint
morethe
effective
combination
of digoxin
with
a CCB.89in patients
reasonableappears
to control
heartthan
ratethe
both
at rest and
during
exercise
with AF.
A combination of digoxin and either a -blocker, diltiazem, or verapamil is
IIaB
IIaB
reasonable to control the heart rate both at rest and during exercise in patients
<<Figure 11>>
with AF.
<<Figure 11>>
46
Figure 11 : Rate control. COPD = chronic obstructive pulmonary disease. *Small doses of b1-elective
Figure
11may
: Rate
control.
COPDif=rate
chronic
obstructive
pulmonary
*Small doses
of b1-elective
blockers
be used
in COPD
control
is not adequate
with disease.
non-dihydropyridine
calcium
channel
blockers
mayand
be digoxin.
used in COPD
if rateiscontrol
is notforadequate
with in
non-dihydropyridine
calcium
channel
antagonists
Amiodarone
also used
rate control
patients who do not
respond
to
antagonists
and
digoxin.
Amiodarone
is
also
used
for
rate
control
in
patients
who
do
not
respond
glycosides, b-blockers or non-dihydropyridine calcium antagonists. Dronedarone may also be used for rateto
glycosides,
b-blockers
or non-dihydropyridine
calcium
antagonists. Dronedarone may also be used for rate
control in patient
with recurrent
episodes of atrial
fibrillation.
control in patient with recurrent episodes of atrial fibrillation.
7.2 NON-PHARMACOLOGICAL RATE CONTROL

7.2.1 AV NODAL ABLATION AND PACING
AV nodal ablation in conjunction with permanent pacemaker implantation
provides highly effective control of the heart rate and improves symptoms, quality
of life, exercise capacity, ventricular function and healthcare utilization in selected
patients with AF.90,100
Ablation of the atrioventricular node is a palliative but irreversible procedure and
is therefore reasonable in patients in whom pharmacological rate control,
including combination of drugs, has failed or rhythm control with drugs and/or LA
ablation has failed.
When the rate of ventricular response to AF cannot be controlled with
pharmacological agents or tachycardia-mediated cardiomyopathy is suspected,
catheter-directed ablation of the AV node may be considered in conjunction with
permanent pacemaker implantation.
It is suggested that programming the pacemaker
initially for the 1 st month post47
ablation to a higher nominal rate (90 beat per minutes) will reduce the risk of
including combination of drugs, has failed or rhythm control with drugs and/or LA
ablation hasAblation
failed.of the atrioventricular node is a palliative but irreversible procedure and
is therefore reasonable in patients in whom pharmacological rate control,
of drugs, has failed or rhythm control with drugs and/or LA

When the including
rate ofcombination
ventricular
response to AF cannot be controlled with
ablation has failed.
pharmacological agents or tachycardia-mediated cardiomyopathy is suspected,
catheter-directed
ablation
AV node
may betoconsidered
conjunction
When the
rate of
of the
ventricular
response
AF cannotinbe
controlled with
with
permanent pharmacological
pacemaker implantation.
agents or tachycardia-mediated cardiomyopathy is suspected,
catheter-directed ablation of the AV node may be considered in conjunction with
permanent
pacemaker implantation.
It is suggested
that programming
the pacemaker initially for the 1 st month postablation to a higher nominal rate (90 beat per minutes) will reducest the risk of
It is suggested that programming the pacemaker initially for the 1 month postsudden cardiac
death.
ablation
to a higher nominal rate (90 beat per minutes) will reduce the risk of
sudden cardiac death.
Keypoints
Ablation of the AV node to control heart rate should be considered when the rate
of thewith
AV node
to control heart rate
should
be considered
the rate
cannot
controlled
pharmacological
agents
and
when AF when
cannot
be
IIaB
IIa B be Ablation
cannot
be controlled
with pharmacological
agents
when AF
cannot
be
prevented by
antiarrhythmic
therapy
or is associated
with and
intolerable
side
effects,
prevented by antiarrhythmic therapy or is associated with intolerable side effects,
and direct catheter-based
or surgical
ablation
of AFofisAF
not
indicated,
has
failed,
or
and
direct
catheter-based
or
surgical
ablation
is
not
indicated,
has
failed,
or
is rejected.90,100
is rejected.90,100
the AV
node should
be considered
for patients
with
permanent AF
AF
Ablation of Ablation
the AVofnode
should
be considered
for patients
with
permanent
IIaB
IIa Ban indication
and an indication
CRT (NYHA
functional
III ambulatory
or ambulatoryclass
class IV
IV
and
for CRTfor(NYHA
functional
classclass
III or
symptoms
despite
optimal
medical
therapy,
LVEF
<35%,
QRS
width
>130
symptoms despite
101-104 optimal medical therapy, LVEF <35%, QRS width >130
101-104 ms).
ms).
Ablation of the AV node should be considered for CRT non-responders in whom
IIaC
Ablation
of AF
theprevents
AV node
shouldbiventricular
be considered
for CRT
in whom
effective
stimulation
and non-responders
amiodarone is ineffective
or
IIa C
AF prevents
effective biventricular stimulation and amiodarone is ineffective or
contraindicated.
contraindicated.
IIaC
In patients with any type of AF and severely depressed LV function (LVEF <35%)
and severe heart failure symptoms (NYHA III or IV), biventricular stimulation
C
with any type of AF and severely depressed LV function (LVEF <35%)
InIIapatients
should be considered after AV node ablation.
and severe heart failure symptoms (NYHA III or IV), biventricular stimulation
AV node
node to
ablation.
Ablation of after
the AV
control heart rate may be considered when
IIbC
IIb
C
tachycardia-mediated cardiomyopathy is suspected and the rate cannot be
pharmacological
direct
ablation
AF is not indicated,
Ablation ofcontrolled
the AVwithnode
to controlagents,
heartand
rate
may
be ofconsidered
when
has failed, or is
rejected.
tachycardia-mediated
cardiomyopathy
is suspected and the rate cannot be
IIbC
IIb C
Ablation of the AV node with consecutive implantation of a CRT device may be

considered in patients with permanent AF, LVEF <35%, and NYHA functional
class I or II symptoms on optimal medical therapy to control heart rate when
pharmacological therapy is insufficient or associated with side effects.
IIb C
In patients with any type of AF, moderately depressed LV function (LVEF <45%)
and mild heart failure symptoms (NYHA II), implantation of a CRT pacemaker
may be considered after AV node ablation.
IIbC
IIb
C
In patients with paroxysmal AF and normal LV function, implantation of a dualchamber (DDDR) pacemaker with mode-switch function may be considered after
AV node ablation.
IIbC
IIb
C
In patients with persistent or permanent AF and normal LV function, implantation

of a single- chamber (VVIR) pacemaker may be considered after AV node
ablation.
IIIC
Catheter ablation of the AV node should not be attempted without a prior trial of
medication, or catheter ablation for AF, to control the AF and/or ventricular rate in
patients with AF.
IIbC
III C
8 MANAGEMENT LONGTERM RHYTHM CONTROL

The term rhythm control encompasses the processes of conversion of atrial
brillation (AF) or atrial utter (AFI) to normal sinus rhythm, as well as the
maintenance of sinus rhythm.
Maintenance of sinus rhythm may also be referred to as prevention of AF/AFI
relapse or recurrence, and may be achieved by pharmacological or
nonpharmacological means, or both (hybrid therapy).
In the absence of spontaneous reversion,
48 cardioversion is chosen as part of the
rhythm-control strategy.
The term
term rhythm
rhythm control
control encompasses
encompasses the
the processes
processes of
of conversion
conversion of
of atrial
atrial
The
brillation (AF)
(AF) or
or atrial
atrial utter
utter (AFI)
(AFI) to
to normal
normal sinus
sinus rhythm,
rhythm, as
as well
well as
as the
the
brillation
maintenance of
of sinus
sinus rhythm.
rhythm.
maintenance
Maintenance of
of sinus
sinus rhythm
rhythm may
may also
also be
be referred
referred to
to as
as
Maintenance
relapse or
or recurrence,
recurrence, and
and may
may be
be achieved
achieved by
by
relapse
nonpharmacological means,
means, or
or both
both (hybrid
(hybrid therapy).
therapy).
nonpharmacological
prevention of
of AF/AFI
AF/AFI
prevention
pharmacological or
or
pharmacological
In the
the absence
absence of
of spontaneous
spontaneous reversion,
reversion, cardioversion
cardioversion is
is chosen
chosen as
as part
part of
of the
the
In
rhythm-control strategy.
strategy.
rhythm-control
The following
following are
are the
the guiding
guiding principles
principles of
of antiarrhythmic
antiarrhythmic drug
drug therapy
therapy to
to
The
maintain sinus
sinus rhythm
rhythm in
in AF:
AF:
maintain
(1) Treatment
Treatment is
is motivated
motivated by
by attempts
attempts to
to reduce
reduce AF-related
AF-related symptoms.
symptoms.
(1)
(2) Efficacy
Efficacy of
of antiarrhythmic
drugs to
to maintain
maintain sinus
sinus rhythm
rhythm is
is modest.
modest.
(2)
(3) Clinically
Clinically successful
successful antiarrhythmic
antiarrhythmic drug
drug therapy
therapy may
may reduce
reduce rather
rather than
than
(3)
eliminate recurrence
recurrence of
of AF.
AF.
eliminate
(4) If
If one
one antiarrhythmic
antiarrhythmic drug
drug fails,
fails, a
a clinically
clinically acceptable
acceptable response
response may
may be
be
(4)
achieved with
with another
another agent.
agent.
achieved
(5) Drug-induced
Drug-induced proarrhythmia
proarrhythmia or
or extra-cardiac
extra-cardiac side
side effects
effects are
are frequent.
frequent.
(5)
(6) Safety
Safety rather
rather than
than efficacy
efficacy considerations
considerations should
should primarily
primarily guide
guide the
the choice
choice
(6)
of antiarrhythmic
antiarrhythmic agent
agent
of
8.1 EFFICACY
EFFICACY OF
OF ANTIARRHYTHMIC
ANTIARRHYTHMIC DRUGS
DRUGS IN
IN PREVENTING
PREVENTING
8.1
RECURRENT ATRIAL
ATRIAL BRILLATION
BRILLATION
RECURRENT
In a
a recent
recent meta-analysis
meta-analysis of
of 44
44 randomized
randomized controlled
controlled trials
trials comparing
comparing
In
105
the antiarrhymic
antiarrhymic drugs
drugs signicantly
signicantly
drugs against
against control,
control,105
the
antiarrhythmic
reduced the
the rate
rate of
of recurrent
recurrent AF.
AF. Overall,
Overall, the
the likelihood
likelihood of
of maintaining
maintaining sinus
sinus
reduced
106
rhythm is
is approximately
approximately doubled
doubled by
by the
the use
use of
of antiarrhythmic
antiarrhythmic drugs.
drugs.106
rhythm
Amiodarone was
was superior
superior to
to class
class II agents
agents and
and sotalol.
sotalol.
Amiodarone
The number
number of
of patients
patients needed
needed to
to treat
treat for
for 1
1 year
year was
was 2
2
9.
9. Withdrawal
Withdrawal due
due to
to
The
side effects
effects was
was frequent
frequent (1
(1 in
in 9
9
27
27 patients),
patients), and
and all
all drugs
drugs except
except amiodarone
amiodarone
side
105
The number
number of
of
and propafenone
propafenone increased
increased the
the incidence
incidence of
of proarrhythmia.
proarrhythmia.105 The
and
patients needed
needed to
to harm
harm was
was 17
17
119.
119. Most
Most of
of the
the trials
trials included
included in
in the
the analysis
analysis
patients
enrolled relatively healthy patients without severe concomitant cardiac disease.
Although mortality was low in all studies (0 4.4%), rapidly dissociating sodium
channel blockers (disopyramide phosphate, quinidine sulfate) were associated
with increased mortality.
8.2 CHOICE OF ANTIARRHYTHMIC DRUGS
Antiarrhythmic therapy for recurrent AF is recommended on the basis of
choosing safer, although possibly less efficacious, medication before resorting to
more effective but less safe therapy. Upon initiation of antiarrhythmic therapy,
regular ECG monitoring is recommended (see Table 16. page 45).
8.2.1 PATIENTS WITH LONE ATRIAL FIBRILLATION
In patients with no or minimal heart disease, -blockers represent a logical rst
attempt to prevent recurrent AF when the arrhythmia is clearly related to mental or
physical stress (adrenergic AF). Flecainide, propafenone, sotalol, or dronedarone
is usually prescribed as second line agents (Figure 12, page 50).107,108
<<Figure 12>>
49
enrolled relatively healthy patients

without
concomitant cardiac disease.
No or minimal
structuralsevere
heart disease
enrolled relatively
without
concomitant
cardiac disease.
Although
mortality healthy
was lowpatients
in all studies
(0 severe
4.4%),
rapidly dissociating
sodium
Althoughblockers
mortality (disopyramide
was low in all phosphate,
studies (0 quinidine
4.4%), rapidly
dissociating
sodium
channel
sulfate)
were associated
channel
blockers
(disopyramide phosphate, quinidine sulfate) were associated
with
increased
mortality.
with increased
mortality.
Adrenergically
mediated
Undetermined
Antiarrhythmic therapy
Dronedaroneon the basis of
B-Blocker for recurrent AF is recommended
Flecainidebefore
Antiarrhythmic
recurrent
AF is recommended
on theresorting
basis to
of
choosing safer, therapy
although for
possibly
less efficacious,
medication
Propafenone
choosing
safer,
although
possibly
less
efficacious,
medication
before resorting
to
more effective but less safe therapy. Upon initiation of Sotalol
antiarrhythmic
therapy,
more effective
but less is
safe
therapy. Upon
antiarrhythmic
therapy,
regular
ECG monitoring
recommended
(seeinitiation
Table 16.ofpage
45).
Sotalol is recommended (see Table 16. page 45).
regular ECG monitoring
Amiodarone
In patients withDronedarone
no or minimal heart disease, -blockers
represent a logical rst
In patients
with norecurrent
or minimal
-blockers
represent
attempt
to prevent
AF heart
when disease,
the arrhythmia
is clearly
relatedatological
mentalrst
or
attempt tostress
prevent
recurrentAF).
AF when
the arrhythmia
is clearly
related
to mental or
physical
(adrenergic
Flecainide,
propafenone,
sotalol,
or dronedarone
physical
(adrenergic
AF).line
Flecainide,
propafenone,
or dronedarone
is
usuallystress
prescribed
as second
agents (Figure
12, pagesotalol,
50).107,108
is usually prescribed as second line agents (Figure 12, page 50).107,108
Figure 12. Choice of antiarrhythmic medication for the patient with AF and no or minimal structural heart
<<Figure
12>> may be initially based on the pattern of arrhythmia onset. Antiarrhythmic agents are
disease. Medication
<<Figure
12>> order within each treatment box.
listed in alphabetical
Adapted with modification from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European
heart Journal 2010; doi:10.1093/eurheartj/ehq278)

8.2.2
PATIENTS WITH UNDERLYING HEART DISEASE
8.2.2 PATIENTS WITH UNDERLYING HEART DISEASE
Cardiovascular disease has conventionally been divided into a variety of
Cardiovascular disease
has conventionally
been divided
a variety
of
pathophysiological
substrates:
hypertrophy, ischaemia,
and into
congestive
heart
pathophysiological
and congestive
heart
failure
(Figure 13). substrates:
For each ofhypertrophy,
these it has ischaemia,
been recommended
that specic
failure be
(Figure
13). For each of these it has been recommended that specic
drugs
avoided.
drugs be avoided.
<<Figure 13>>
<<Figure 13>>
Individual drugs and their main disadvantages are listed in Table 17.
Amiodarone is the most efficacious antiarrhythmic drug for the prevention of
105,109-111
Amiodarone
the mostseveral
efficacious
antiarrhythmic
drug
for failed
the prevention
have
to identify of
a
recurrent AF.isHowever,
meta-analyses
105,109-111
haveInfailed
to the
identify
a
recurrent AF.
However,
severalon
meta-analyses
benecial
effect
of amiodarone
cardiovascular outcomes.
view of
better
benecial
of amiodarone
on cardiovascular
In view ofas
thethe
better
safety
andeffect
potential
outcome benet,
dronedaroneoutcomes.
may be preferable
rst
safety
and potential
outcome
dronedarone
may be preferable
the rst
antiarrhythmic
option,
at leastbenet,
in patients
with symptomatic
AF and as
underlying
antiarrhythmic option,
at least
in patients
with symptomatic
AF and symptoms,
underlying
cardiovascular
disease.
Should
dronedarone
fail to control
cardiovascular
disease.
Should dronedarone fail to control symptoms,
amiodarone
might
then be necessary.
amiodarone might then be necessary.
Dronedarone can be used safely in patients with ACS, chronic stable angina,
Dronedarone heart
can be
used safely
in patients
with only
ACS,bechronic
stable
angina,
hypertensive
disease.
Dronedarone
should
used in
maintaining
hypertensive
heartin disease.
Dronedarone
should
used inDronedarone
maintaining
sinus
rhythm and
whose normal
heart rhythm
hasonly
beenberestored.
sinus rhythm
normal
has been restored. Dronedarone
should
not beand
usedininwhose
patients
with heart rhythm
failure.112
should not be used in patients with heart failure.112
Figure 13. Choice of antiarrhythmic drug according to underlying pathology. ACEI=angiotensin-converting enzyme inhibitor; ARB=
angiotensin receptor blocker; CAD = coronary artery disease; CHF=congestive heart failure; HT=hypertension; LVH =left ventricular
hypertrophy; NYHA=New York Heart Association; unstable=cardiac decompensation within the prior 4 weeks. Antiarrhythmic agents
are listed in alphabetical order within each treatment box. ? = evidence for upstream therapy for prevention of atrial remodelling still
remains controversial.
Adapted with modification from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal
50
Cardiovascular disease has conventionally been divided into a variety of

pathophysiological substrates: hypertrophy, ischaemia, and congestive heart
failure (Figure 13). For each of these it has been recommended that specic
drugs be avoided.
<<Figure 13>>
Amiodarone is the most efficacious antiarrhythmic drug for the prevention of
recurrent AF. However, several meta-analyses105,109-111 have failed to identify a
benecial effect of amiodarone on cardiovascular outcomes. In view of the better
safety and potential outcome benet, dronedarone may be preferable as the rst
antiarrhythmic option, at least in patients with symptomatic AF and underlying
cardiovascular disease. Should dronedarone fail to control symptoms,
amiodarone might then be necessary.
Dronedarone can be used safely in patients with ACS, chronic stable angina,
hypertensive heart disease. Dronedarone should only be used in maintaining
sinus rhythm and in whose normal heart rhythm has been restored. Dronedarone
should not be used in patients with heart failure.112
8.2.2.1 Patients with left ventricular hypertrophy
In patients with LV hypertrophy, sotalol is thought to be associated with an
increased incidence of proarrhythmia. Flecainide and propafenone may be used,
but there is some concern about proarrhythmic risk, especially in patients with
marked hypertrophy (LV wall thickness
>1.4 cm according to previous
guidelines), and associated coronary artery disease.
Since dronedarone was demonstrated to be safe and well tolerated in a large
study including patients with hypertension and possible LV hypertrophy, it is an
option for this population, although denitive data do not exist. Amiodarone
should be considered when symptomatic AF recurrences continue to impact on
the quality of life of these patients.
8.2.2.2 Patients with coronary artery disease
Patients who have coronary artery disease should not receive ecainide163 or
propafenone. Sotalol or dronedarone should be administered as rst-line therapy.
Dronedarone may be preferred based on its safety prole. Amiodarone is
considered as the drug of last resort in this population due to its extra-cardiac
side effect prole.
8.2.2.3 Patients with heart failure
Amiodarone is the only agents available in Malaysia that can be safely
administered in patients with heart failure.
Dronedarone is contraindicated in patients with all classes of heart failure.112 In
such patients, amiodarone should be used.
The following antiarrhythmic drugs are recommended for rhythm control in
patients with AF, depending on underlying heart disease:
IA
x amiodarone21,105,113
IA
x dronedarone85,86
IA
x ecainide105,114
IA
x propafenone105,113
51
sideside
effect
effect
prole.
prole.
Amiodarone is the only agents available in Malaysia that can be safely

administered
in Patients
patients
with
heart
failure.
8.2.2.3
8.2.2.3
Patients
with
with
heart
heart
failure
failure
112
Amiodarone
Amiodarone
is is
thethe
onlyonly
agents
available
available
Malaysia
Malaysia
thatheart
that
cancan
be be
safely
safely
In
Dronedarone
is contraindicated
in agents
patients
with in
all in
classes
of
failure.
administered
administered
in patients
in patients
withwith
heart
failure.
failure.
such patients,
amiodarone
should
beheart
used.
112 112
In In
Dronedarone
Dronedarone
is contraindicated
is contraindicated
in patients
in patients
withwith
all all
classes
classes
of heart
of heart
failure.
failure.
such
such
patients,
patients,
amiodarone
amiodarone
should
should
be be
used.
used.
The following antiarrhythmic drugs are recommended for rhythm control in

patients with AF, depending on underlying heart disease:
TheThe
following
following
antiarrhythmic
antiarrhythmic
drugs
drugs
areare
recommended
recommended
for for
rhythm
rhythm
control
control
in in
patients
patients
withwith
AF,AF,
depending
depending
on on
underlying
underlying
heart
heart
disease:
disease:
Keypoints
x amiodarone21,105,113
IA
I AIA
21,105,113
21,105,113
x amiodarone
x amiodarone
x dronedarone85,86
85,8685,86
x dronedarone
x dronedarone
IA
I AIA
x ecainide105,114 105,114
105,114
x ecainide
x ecainide
I AIA
IA
105,113
105,113
105,113
I AIA
IxApropafenone
x propafenone
x propafenone
21,48,105 21,48,105
21,48,105
IxAd,I-sotalol
I AIA
x d,I-sotalol
x d,I-sotalol
IA/C
I A/C
Amiodarone is more effective in maintaining sinus rhythm than sotalol,

propafenone, ecainide (by analogy), or dronedarone (Level of Evidence A), but
because of its toxicity prole should generally be used when other agents have
failed or are contraindicated (Level of Evidence C).21,105,110,113
IB
IB
In patients with severe heart failure, NYHA class III and IV or recently unstable
(decompensation within the prior month) NYHA class II, amiodarone should be
the drug of choice.115
IA
IA
In patients without signicant structural heart disease, initial antiarrhythmic

therapy should be chosen from dronedarone, ecainide, propafenone, and
sotalol.85,86,105,113-115
IC
IC
-Blockers are recommended for prevention of adrenergic AF.
IIa C
IIaC
If one antiarrhythmic drug fails to reduce the recurrence of AF to a clinically

acceptable level, the use of another antiarrhythmic drug should be considered.
IIa B
IIaB
Dronedarone should be considered in order to reduce cardiovascular

hospitalizations in patients with non-permanent AF and cardiovascular risk
factors.85,86
IIaC
IIa C
-blockers should be considered for rhythm (plus rate) control in patients with a
rst episode of AF.
III B
IIIB
Dronedarone is not recommended for treatment of permanent AF and all classes

of heart failure.
III C
IIIC
Antiarrhythmic drug therapy is not recommended for maintenance of sinus

rhythm in patients with advanced sinus node disease or AV node dysfunction
unless they have a functioning permanent pacemaker.
8.3 NONPHARMACOLOGICAL THERAPY

There is a variety of alternative non-pharmacological therapies for the prevention
and control of AF.
8.3.1 LEFT ATRIAL CATHETER ABLATION
Catheter ablation of AF particularly circumferential pulmonary vein ablation
(isolation) in the left atrium represents a promising and evolving therapy for
selected patients resistant to pharmacological therapy.
Ablation is indicated in highly symptomatic, paroxysmal or persistent AF, despite
optimal medical therapy and in patients with minimal or moderate structural heart
disease.
52
A recent meta-analysis found a 77% success
rate for catheter ablation strategies
vs. 52% for antiarrhythmic medication.117 Similar results have been reported in
Catheter ablation of AF particularly circumferential pulmonary vein ablation

(isolation) in the left atrium represents a promising and evolving therapy for
selected patients resistant to pharmacological therapy.
Ablation is indicated in highly symptomatic, paroxysmal or persistent AF, despite
optimal medical therapy and in patients with minimal or moderate structural heart
disease.
A recent meta-analysis found a 77% success rate for catheter ablation strategies
vs. 52% for antiarrhythmic medication.117 Similar results have been reported in
other meta-analyses,118,-120 one of which showed that PV isolation for paroxysmal
or persistent AF was associated with markedly increased odds of freedom from
AF at 1 year.119
Ablation may particularly benefit younger patients with lone AF who are
frequently symptomatic and for whom long-term antiarrhythmic poses higher risk
and lifestyle cost.
Figure 14. Choice between ablation and antiarrhythmic drug therapy for patients with and without structural heart disease. Proposed integration
of antiarrhythmic drug and catheter ablation for AF in patients with relevant underlying heart disease and for those with no or minimal heart
disease, including hypertension (HT) without left ventricular hypertrophy (LVH). More extensive LA ablation may be needed; *usually PVI is
appropriate. AF= atrial fibrillation; CAD = coronary artery disease; CHF = congestive heart failure; HT=hypertension; LVH=left ventricular
hypertrophy; NYHA=New York Heart Association; PVI=pulmonary vein isolation. Antiarrhythmic agents are listed in alphabetical order within
each treatment box. Please note that left atrium (LA) ablation as first-line therapy (dashed line) is a Class IIb recommendation for patients with
paroxysmal AF and no or minimal heart disease, who remain highly symptomatic, despite rate control, and who reject antiarrhythmic drug
therapy.
<<Figure 14>>
Adapted with modification from the ESC Guidelines for the Management of Atrial Fibrillation (2010 Version) (European heart Journal 2010;
For patients with either persistent AF or long-standing persistent AF, and no or

minimal organic heart disease, the treatment strategies and the benet risk
ratio of catheter ablation are less well established. Extensive and frequently
repeated ablation procedures may be necessary in these patients, and it seems
reasonable to recommend that they should be refractory to antiarrhythmic drug
treatment before ablation is considered (See Figure 14).
For symptomatic paroxysmal and persistent AF in patients with relevant organic

heart disease, antiarrhythmic drug treatment is recommended before catheter
ablation. In such patients, successful ablation is more difficult to achieve. Major
symptoms should be associated with the arrhythmia to justify the procedure.
Ablation of persistent and long-standing persistent AF is associated with variable
but encouraging success rates, but very often requires several attempts.
IB
IIa A
Ablation of common atrial utter is recommended as part of an AF ablation

procedure if documented prior to the ablation procedure or occurring during the
AF ablation.18
Catheter ablation for paroxysmal AF should be considered in symptomatic
53
Ablationheart
may disease,
particularlythe
benefit
younger
patients and
with the
lone benet
AF who are
minimal organic
treatment
strategies
risk
frequently symptomatic and for whom long-term antiarrhythmic poses higher risk
ratio of catheter
ablation
are
less
well
established.
Extensive
and
frequently
and lifestyle cost.
reasonableFor
to patients
recommend
that persistent
they should
refractory to
antiarrhythmic
drug
with either
AF orbe
long-standing
persistent
AF, and no
or
minimalablation
organic heart
disease, the
treatment
and the benet risk
treatment before
is considered
(See
Figure strategies
14).
ratio of catheter ablation are less well established. Extensive and frequently

<<Figure 14>>
reasonable to recommend that they should be refractory to antiarrhythmic drug
treatment before ablation is considered (See Figure 14).
For symptomatic paroxysmal and persistent AF in patients with relevant organic

heart disease,
antiarrhythmic
drug treatment is recommended before catheter
<<Figure
14>>
For
symptomatic
paroxysmal
and the
persistent
AF in patients
with the
relevant
organic
symptoms should be associated with
arrhythmia
to justify
procedure.
disease,
antiarrhythmic
drugpersistent
treatment AF
is recommended
Ablation ofheart
persistent
and
long-standing
is associatedbefore
with catheter
variable
but encouraging
success
but very often
requires
several
attempts.
symptoms
shouldrates,
be associated
with the
arrhythmia
to justify
the procedure.
Ablation of persistent and long-standing persistent AF is associated with variable
Ablation ofbutcommon
atrial
utter
is but
recommended
as part
of attempts.
an AF ablation
encouraging
success
rates,
very often requires
several
Keypoints
18
Ablation of common atrial utter is recommended as part of an AF ablation
AF ablation.
IIB
B
AF ablation.18

IIaA
IIa
A

patients who have previously failed a trial of antiarrhythmic medication.31,117,122-125
IIaB
IIa
B
Ablation of persistent symptomatic AF that is refractory to antiarrhythmic therapy

should be considered a treatment option.18
IIaC
IIa
C
In patients post-ablation, LMWH or i.v. UFH should be considered as bridging

therapy prior to resumption of systemic OAC, which should be continued for a
minimum of 3 months. Thereafter, the individual stroke risk factors of the patient
should be considered when determining if OAC therapy should be continued.
IIaB
IIa
B
Continuation of OAC therapy postablation is recommended in patients with 1

major (denitive) or >2 clinically relevant non-major risk factors (i.e. CHA
126
2DS2-VASc score >2).
IIbC
IIb
C
Catheter ablation of AF may be considered in patients with symptomatic longstanding persistent AF refractory to antiarrhythmic drugs.
IIbB
IIb
B
Catheter ablation of AF in patients with heart failure may be considered when

antiarrhythmic medication, including amiodarone, fails to control symptoms.29,30
IIbB
IIb
B
Catheter ablation of AF may be considered prior to antiarrhythmic drug therapy in

symptomatic patients despite adequate rate control with paroxysmal symptomatic
AF and no signicant underlying heart disease.117
8.3.2 SURGICAL ABLATION

The major 8.3.2
indication
for surgical
ablation of AF is the presence of both AF and
SURGICAL
ABLATION
the requirement for cardiac surgery for structural heart disease.120,127,128 Standalone surgery
for AFindication
shouldfor
besurgical
considered
symptomatic
AF ofpatients
The major
ablationfor
of AF
is the presence
both AF who
and
120,127,128
the requirement
forhave
cardiac
surgery
heart disease.
Standprefer a surgical
approach,
failed
one for
or structural
more attempts
at catheter ablation,
surgery for for
AFcatheter
should be
considered for symptomatic AF patients who
or who are alone
not candidates
ablation.
prefer a surgical approach, have failed one or more attempts at catheter ablation,
or who are not candidates for catheter ablation.
Keypoints
Surgical ablation of AF should be considered in patients with symptomatic AF
120,127,128
undergoingSurgical
cardiacablation
surgery.
of AF should be considered in patients with symptomatic AF
IIaA
IIa A
120,127,128
undergoing cardiac surgery.
Surgical ablation of AF may be performed in patients with asymptomatic AF

Surgical ablation of AF may be performed in patients with asymptomatic AF
undergoing
cardiac surgery if feasible with minimal risk.
IIbC
IIb
C
undergoing cardiac surgery if feasible with minimal risk.
Minimally invasive
ablationablation
of AF of
without
concomitant
cardiac
is
Minimallysurgical
invasive surgical
AF without
concomitant
cardiacsurgery
surgery is
feasible
may be
in patients
with with
symptomatic
AFAFafter
of
feasible
and performed
may be performed
in patients
symptomatic
afterfailure
failure of
IIbC
IIb C and
catheter ablation.
catheter ablation.
8.3.3 SUPPRESSION OF AF THROUGH PACING
8.3.3 SUPPRESSION
OF AF THROUGH
54 PACING
Several studies have examined the role of atrial pacing to prevent recurrent
IIb C
Surgical ablation
AF may
performed
in patients
with with
asymptomatic
Surgical of
ablation
of AFbe
should
be considered
in patients
symptomatic AF
AF
IIa A
120,127,128
undergoing
cardiac surgery
if feasible
with minimal risk.
undergoing
cardiac surgery.
IIb C
Surgical ablation
AF mayofbeAF
performed
in patients with
asymptomatic
Minimally invasive
surgicalofablation
without concomitant
cardiac
surgeryAF
is
IIb C
undergoing
surgery
feasible with
risk.
feasible and
may becardiac
performed
inifpatients
withminimal
symptomatic
AF after failure of
catheter ablation.
Minimally invasive surgical ablation of AF without concomitant cardiac surgery is
IIb C
feasible and may be performed in patients with symptomatic AF after failure of
8.3.3 SUPPRESSION
OF AF THROUGH PACING
catheter ablation.
8.3.3 SUPPRESSION
OF AF
PACING
Several studies
have examined
theTHROUGH
role of atrial
pacing to prevent recurrent
paroxysmal AF. In patients with symptomatic bradycardia, the risk of AF is lower
Several studies have examined129
the role of atrial pacing to prevent recurrent
with atrial than with ventricular pacing. In patients with sinus node dysfunction
paroxysmal AF. In patients with symptomatic bradycardia, the risk of AF is lower
129 randomized trials support atrial or
frompacing.
several
and normalwith
AVatrial
conduction,
than with data
ventricular
In patients with sinus node
dysfunction
dual-chamber
ventricular
pacing
for prevention
oftrials
AF.130-133
data
from several
randomized
supportPatients
atrial or
and rather
normal than
AV conduction,
with paroxysmal
AF rather
and symptomatic
shouldof be
referred
for
dual-chamber
than ventricular bradycardia
pacing for prevention
AF.130-133
Patients
with paroxysmal
and symptomatic
bradycardia
should be referred for
electrophysiological
review AF
for consideration
of atrial
based pacing.
electrophysiological review for consideration of atrial based pacing.
IIaB
Keypoint
When ventricular
pacing with dual-chamber devices is unavoidable because of
When ventricular pacing with dual-chamber devices is unavoidable because of
IIaB
IIaB
concomitant
disease of
the AV
system,
the the
evidence
is isless
concomitant
disease
of conduction
the AV conduction
system,
evidence
lessclear
clear that
that
pacing ispacing
superior.
Although
atrial-based
pacing
is associated
a
atrial-basedatrial-based
is superior.
Although
atrial-based
pacing
is associatedwith
with a
lowerofburden
of AF
and stroke
risk compared
to ventricular-basedpacing
pacing in
in
lower burden
AF and
stroke
risk compared
to ventricular-based
pacing as
as a
patients requiring
pacemakers
for bradyarrhythmias,
value
ofofpacing
a
patients requiring
pacemakers
for bradyarrhythmias,
the the
value
primaryfor
therapy
for prevention
of recurrent
AF not
has been
not been
proven.
primary therapy
prevention
of recurrent
AF has
proven.
8.4 UPSTREAM THERAPY

Upstream therapy is a term used that relates to prevention or delaying of
myocardial remodelling associated with hypertension, heart failure, or
inammation (e.g. after cardiac surgery) and therefore may deter the
development
new AF THERAPY
(primary prevention) or, once established, its rate of
8.4 of
UPSTREAM
recurrence or progression to permanent AF (secondary prevention).135
Upstream therapy is a term used that relates to prevention or delaying of
remodelling associated
with inhibitors
hypertension,
heart angiotensin
failure, or
Treatmentsmyocardial
with angiotensin-converting
enzyme
(ACEIs),
inammation (e.g. after cardiac surgery) and therefore may deter the
receptor blockers
(ARBs), aldosterone antagonists, statins, and omega-3
development of new AF (primary prevention) or, once established, its rate of
polyunsaturated
fattyor progression
acids (PUFAs)
are usually
referred
to as 135upstream
recurrence
to permanent
AF (secondary
prevention).
therapies for AF.
Treatments with angiotensin-converting enzyme inhibitors (ACEIs), angiotensin
receptor blockers (ARBs), aldosterone

antagonists, statins,
8.4.1 ANGIOTENSIN-CONVERTING
ENZYME INHIBITORS
AND and omega-3
polyunsaturated
fattyBLOCKERS
acids (PUFAs) are usually referred to as upstream
ANGIOTENSIN
RECEPTOR
therapies for AF.
Primary prevention
8.4.1 ANGIOTENSIN-CONVERTING ENZYME INHIBITORS AND
ANGIOTENSIN RECEPTOR BLOCKERS
In patients with congestive cardiac failure, several meta-analyses have shown

a signicant
30 prevention
48% reduction in risk of AF associated with ACEI and ARB
Primary
therapies.136-140
In patients with congestive cardiac failure, several meta-analyses have shown
a signicant 30 48% reduction in risk of AF associated with ACEI and ARB

While in patients
with hypertension, in meta-analyses, the overall trend was in
therapies.136-140
favour of ACEI- or ARB-based therapy, but only one meta-analysis has shown a
statistically While
signicant
25%with
reduction
in RR of
AF.138the overall trend was in
in patients
hypertension,
in incident
meta-analyses,
favour of ACEI- or ARB-based therapy, but only one meta-analysis has shown a
IIa A
IIa B
signicant
reduction infor
RR prevention
of incident AF.
ACEIs andstatistically
ARBs should
be25%
considered
of138new-onset AF in
Keypoints
patients with heart failure and reduced ejection fraction.136-140
ACEIs and ARBs should be considered for prevention of new-onset AF in
IIaA
IIa
A
138,141,142
patients with
hypertension,
with left ventricular
hypertrophy.
ACEIs
and ARBs particularly
for prevention
of new-onset AF in
IIaB
IIa
B
138,141,142
patients with hypertension, particularly with left ventricular hypertrophy.
III C
Upstream therapies with ACEIs, ARBs, and statins are not recommended for
primary
IIIC
III
C prevention of AF in patients without cardiovascular disease.
primary prevention of AF in patients without cardiovascular disease.
Secondary prevention
55
Several relatively
small prospective
randomized
controlled
Several relatively
small prospective
randomized
controlled trials
trials have
have
demonstrated
that therapy
ACEI/ARB
conferred
an additional
benet
demonstrated
that with
therapy
with ACEI/ARB
conferred
an additional
beneton
onrisk
risk

patients with hypertension, particularly with left ventricular hypertrophy.138,141,142
primary prevention of AF in patients without cardiovascular disease.
Several relatively small prospective randomized controlled trials have
demonstrated that therapy with ACEI/ARB conferred an additional benet on risk
of recurrent AF after cardioversion when co-administered with antiarrhythmic
drug therapy, usually amiodarone, compared with an antiarrhythmic drug
alone.143,144 Meta-analyses driven by these studies have reported a signicant 45
50% reduction in RR of recurrent AF.136-139 Conversely, a double-blind,
placebo-controlled study failed to demonstrate any benet of therapy with
candesartan for promotion of sinus rhythm after cardioversion in patients who did
not receive antiarrhythmic drug therapy. 145
Evidence to support the use of ACEI/ARB in patients with paroxysmal or
persistent AF who are not undergoing electrical cardioversion remains
controversial.
Evidence
to are
support
theundergoing
use of ACEI/ARB
in patients
with paroxysmal
or
persistent
AFwith
who
notARBs
electrical
remains
Pre-treatment
ACEIs
and
be considered
incardioversion
patients
with recurrent
persistent
AF who
are notmay
undergoing
electrical
cardioversion
remains
controversial.
AF and receiving
antiarrhythmic drug therapy.136-138,143,144
controversial.
Keypoints
Pre-treatment
with
ACEIs
and
may
considered
in patients
with
Pre-treatment
with
ACEIs
andprevention
ARBsbe
may
be
inparoxysmal
patients
withrecurrent
recurrent
Evidence
to
support
the
useARBs
of
ACEI/ARB
inconsidered
patients
with
paroxysmal
ARBs or ACEIs
may
be
useful
for
of
recurrent
AF or or
in
136-138,143,144
136-138,143,144
IIbB
IIb
B receiving
AF
andwho
receiving
antiarrhythmic
drug
therapy.
AF
and
antiarrhythmic
therapy.
persistent
AF
are
not drug
undergoing
electrical
cardioversion
remains
patients
with
persistent
AF
undergoing
electrical
cardioversion
in
the
absence
of
controversial.
signicant structural
heart
disease
ifnotthese
agents are
indicated
for other reasons
persistent
AF who
areuseful
undergoing
electrical
cardioversion
remains
ARBs or
ACEIs
be
for
prevention
of recurrent
paroxysmal AF
AF
or in
136,146,147
ARBs
or ACEIs
may
be may
useful
for prevention
of recurrent
paroxysmal
or
in
(e.g.
hypertension).
controversial.
patients
with persistent AF undergoing electrical cardioversion in the absence of
IIbB
IIb
B
patients
with
persistent
AF
undergoing
electrical
cardioversion
in
the
absence
of
Pre-treatment
with
ACEIs
and
ARBs
may
be
considered
in
patients
with
recurrent
signicant structural heart disease if these
agents are indicated for other reasons
136-138,143,144
136,146,147
signicant
structural
heart
if these
agents
are indicated
for other
reasons
Pre-treatment
withdisease
ACEIs
and
ARBs
may
be considered
in patients
with recurrent
AF and receiving
antiarrhythmic
drug
therapy.
(e.g.
hypertension).
136,146,147
IIb Bhypertension).
AF and receiving
antiarrhythmic drug therapy.136-138,143,144
(e.g.
8.4.3
STATINS
ARBs or ACEIs may be useful for prevention of recurrent paroxysmal AF or in
ARBsSTATINS
or ACEIs may be useful for prevention of recurrent
paroxysmal AF or in
8.4.3
148
patients
with
persistentpersistent
AFa undergoing
electrical
cardioversion
the absence
of
For
post-operative
recent
systematic
review,
have in
reported
a lower
patients withAF,
AF undergoing
electrical
cardioversion
in the absence
of
IIb BSTATINS
8.4.3
signicant
structural
heart
disease
if
these
agents
are
indicated
forreported
other
reasons
148
incidence signicant
of new
onset
AF
favouring
statins.
Some
studies,
particularly
in
structural
heart
disease
if
these
agents
are
indicated
for
other
reasons
For
post-operative
AF,
a
recent
systematic
review,
have
a
lower
136,146,147136,146,147
(e.g.
hypertension).
(e.g.
patients
with
LVhypertension).
dysfunction
and heart
failure, statins.
have shown
20 50%
reduction
incidence
of new onset
AF favouring
Some astudies,
particularly
in
149systematic review,148 have reported a lower
For
post-operative
AF,
a
recent
in the incidence
ofwith
new-onset
AF. and heart failure, have shown a 20 50% reduction
patients
LV dysfunction
incidence of
new
onsetof AF
favouring
in the
incidence
new-onset
AF.149 statins. Some studies, particularly in
8.4.3
STATINS
patients
with
LV
dysfunction
and
heart
failure, have
shown a 20
8.4.3
STATINS
Statins
should be considered for
prevention
of new-onset
AF 50%
after reduction
coronary
Statinsofshould
be considered
prevention of new-onset
AF after coronary
in
the
new-onset
AF.149
artery
bypass
grafting,
isolated
orrecent
inforcombination
with148valvular
interventions.
IIa
B incidence
For
post-operative
AF,
a
systematic
review,
have
reported
a lower
artery bypass grafting, isolated or in combination
148with valvular interventions.
148,150
For post-operative
recentAFsystematic
review,Some
have
reported
a lower
148,150
incidence ofAF,
newa onset
favouring statins.
studies,
particularly
in
Statins
should
bewith
considered
for and
prevention
of Some
new-onset
after
incidence
of new
onset
AF favouring
statins.
studies,
particularly
in
patients
LV dysfunction
heart
failure,
have shown
aAF
20
50% coronary
reduction
149
artery
or
in failure,
combination
with valvular
interventions.
in
the
incidence
ofconsidered
new-onset
AF.
Keypoints
patientsbypass
with
LV
dysfunction
and
aAF
20
in
50%
reduction
Statins
may
begrafting,
considered
for heart
prevention
ofhave
new-onset
patients
with
Statins
may beisolated
for
prevention
of shown
new-onset
AFin
patients
with
148,150
149
IIb B
151,152
151,152
underlying
heart disease,
failure.
in
the incidence
new-onset
AF.particularly
underlying
heart of
disease,
particularly
heart heart
failure.
IIaB
IIa
B
Statins should be considered for prevention of new-onset AF after coronary
artery
bypass
grafting, isolated orFATTY
in combination
with
valvular
interventions.
8.4.4
POLYUNSATURATED
ACIDS
AND
Statins
bebe
considered
of ofnew-onset
AF
inALDOSTERONE
patients
with
should
consideredforforprevention
preventionACIDS
new-onset
AF
after
coronary
148,150
8.4.4 may
POLYUNSATURATED
FATTY
AND
ALDOSTERONE
ANTAGONIST
underlying
heartgrafting,
disease,isolated
particularly
heart
failure.151,152
artery
bypass
or in
combination
with valvular interventions.
ANTAGONIST
148,150
Statins
maythere
be is
considered
prevention
of any
new-onset
AF in patients
At present,
no robust for
evidence
to make
recommendation
for the with
use
IIbB
IIb
B
151,152
8.4.4
POLYUNSATURATED
FATTY
ACIDS
AND prevention
ALDOSTERONE
underlying
heart
disease,
particularly
heart
failure.
At present,
there
is or
no
robust
evidence
to for
make
anyorrecommendation
for ofthe
of
PUFAs
aldosterone
antagonist
primary
secondary
AF.use
ANTAGONIST
Statins
may
be considered
for prevention
of ornew-onset
in patients
with
of PUFAs
or aldosterone
antagonist
for primary
secondaryAF
prevention
of AF.
151,152
8.4.4
POLYUNSATURATED
FATTY
ACIDS
AND
ALDOSTERONE
underlying heart disease, particularly heart failure.
At present,ANTAGONIST
there is no robust evidence to make any recommendation for the use
of
PUFAs
or
aldosterone antagonistFATTY
for
primary
or secondary
prevention
of AF.
8.4.4
POLYUNSATURATED
ACIDS
ALDOSTERONE
At present, there is no robust
evidence to
make any AND
recommendation
for the use
ANTAGONIST
of PUFAs or aldosterone antagonist for primary or secondary prevention of AF.
At present, there is no robust evidence to make any recommendation for the use
of PUFAs or aldosterone antagonist for primary or secondary prevention of AF.
56
9 MANAGEMENT SPECIAL POPULATIONS

9.1 POST-OPERATIVE AF
Although AF may occur after noncardiac surgery, the incidence of atrial
arrhythmias including AF after open-heart surgery is between 20% and 50%.
Post-operative AF usually occurs within 5 d of open-heart surgery, with a peak
incidence on the second day. The arrhythmia is usually self-correcting, and sinus
rhythm resumes in more than 90% of patients by 6 to 8 wk after surgery.
A systematic review of 58 studies in 8565 patients has shown that interventions
to prevent and/or treat post-operative AF with -blockers, sotalol, or amiodarone
and, less convincingly, atrial pacing, are favoured with respect to outcome. 153
9.1.1 PREVENTION OF POST-OPERATIVE ATRIAL FIBRILLATION
-Blocker therapy is most effective when provided both before and after cardiac
surgery compared with only before or after surgery.153-155 Withdrawal of blockers is a signicant risk factor for the development of post-operative AF and
should be avoided. Treatment should be started at least 1 week before surgery
with a -blocker without intrinsic sympathomimetic activity.
Prophylactic amiodarone decreased the incidence of post- operative AF156. The
benecial effect of amiodarone has been consistently demonstrated in a
systematic review.153The adverse effects of perioperative prophylactic i.v.
amiodarone include an increased probability of post-operative bradycardia and
hypotension.153
Sotalol has been reported to reduce the incidence of post-operative AF by 64%
compared with placebo.153 However, the use of sotalol places patients at risk of
bradycardia and torsade de pointes, especially those with electrolyte
disturbances, and its use in post-operative AF is limited.
Meta-analyses demonstrated that corticosteroid therapy was associated with a
26 45% reduction in post-operative AF and shorter hospital stay. 157 However,
the potential adverse effects on glucose metabolism, wound healing, and
infection, make their use for prevention of AF as controversial.
One meta-analysis of eight trials has shown that prophylactic atrial pacing
reduced the incidence of post-operative AF regardless of the atrial pacing site or
pacing algorithm used. 153
9.1.2 TREATMENT OF POST-OPERATIVE ATRIAL FIBRILLATION
In haemodynamically stable patients, the majority will convert spontaneously to
sinus rhythm within 24 h. Initial management includes correction of predisposing
factors (such as pain management, haemodynamic optimization, weaning of i.v.
inotropes, correcting electrolytes and metabolic abnormalities, and addressing
anaemia or hypoxia) where possible.158
In the highly symptomatic patient or when rate control is difficult to achieve,
cardioversion may be performed. DCCV is 95% successful but pharmacological
cardioversion is more commonly used. Amiodarone was shown to be more
effective than placebo in converting post-operative AF to sinus rhythm.
57
Short-acting -blockers (e.g. esmolol) are particularly useful when
factors (such as pain management, haemodynamic optimization, weaning of i.v.

factors
as pain management,
optimization,
weaning of i.v.
cardioversion
may(such
be performed.
DCCV ishaemodynamic
95% successful
but pharmacological
cardioversion
is more commonly used. Amiodarone was shown to be more
effective than placebo in converting post-operative AF to sinus rhythm.
may be
performed.
DCCV are
is 95%particularly
successful but useful
pharmacological
Short-actingcardioversion
-blockers
(e.g.
esmolol)
when
cardioversion
is more
was shown
be more
haemodynamic
instability
is a commonly
concern. used.
OtherAmiodarone
atrioventricular
nodalto blocking
effective
than
placebo
in
converting
post-operative
AF
to
sinus
rhythm.
agents, such as non-dihydropyridine calcium channel antagonists, can be used
as alternatives,
but digoxin is less effective when adrenergic tone is high. The
Short-acting -blockers (e.g. esmolol) are particularly useful when
agents usedhaemodynamic
for rate control
of AF following
cardiac
surgery
are listednodal
in Table
15.
instability
is a concern.
Other
atrioventricular
blocking
agents, such as non-dihydropyridine calcium channel antagonists, can be used
A number as
of alternatives,
studies have
increased
stroke intone
patients
but shown
digoxin an
is less
effective risk
whenofadrenergic
is high.after
The
agents used
for rate controlwith
of AFheparin
followingor
cardiac
are listed inwhen
Table AF
15.
cardiac surgery.
Anticoagulation
VKAsurgery
is appropriate
persists longer than 48 h.159 Standard precautions regarding anticoagulation
A number of studies have shown an increased risk of stroke in patients after
pericardioversion
should be used (see Section 4.3).
cardiac surgery. Anticoagulation with heparin or VKA is appropriate when AF

persists longer than 48 h.159 Standard precautions regarding anticoagulation
pericardioversion should be used (see Section 4.3).
Keypoints
Oral
-blockers are recommended to prevent post-operative AF for patients
undergoing cardiac surgery in the absence of contraindications.153,154
I AIA
Oral -blockers are recommended to prevent post-operative AF for patients

153,154
undergoing
cardiac
in the absence ofdrugs
contraindications.
If used, -blockers
(or
othersurgery
oral antiarrhythmic
for AF management) are
154,155
recommended
to
be
continued
until
the
day
of
surgery.
If used, -blockers (or other oral antiarrhythmic drugs for AF management) are
I BIB
recommended to be continued until the day of surgery. 154,155
Restoration of sinus rhythm by DCCV is recommended in patients who develop

sinus
rhythm by DCCV isunstable.
recommended in patients who develop
Restoration
post-operative
AF andofare
haemodynamically
I CIC
post-operative AF and are haemodynamically unstable.
Ventricular rate control is recommended in patients with AF without

Ventricular rate 155control is recommended in patients with AF without
I BIB
haemodynamic
instability.
haemodynamic instability.155
Pre-operative
administration
of amiodarone
should
be considered
asasprophylactic
Pre-operative
administration
of amiodarone
should
be considered
prophylactic
IIa
A
IIaA
therapy
for therapy
patientsforatpatients
high risk
for post-operative
AF.153,154,160
at high
risk for post-operative
AF.153,154,160
Unless contraindicated,
antithrombotic/anticoagulation
medication for
for postpostUnless
contraindicated,
antithrombotic/anticoagulation
medication
IIa
A
IIaA
159
operative AF should be considered when the duration of AF is >48 hours.
operative AF
should be considered when the duration of AF is >48 hours.159
If sinus rhythm is restored successfully, duration of anticoagulation should be for
B
IIaB
If IIa
sinus
rhythm
is restored
duration
of anticoagulation
be risk
for
a minimum
of 4 successfully,
weeks but more
prolonged
in the presenceshould
of stroke
a minimumfactors.
of 4159weeks but more prolonged in the presence of stroke risk
159
factors.
IIa
C
IIaC
Antiarrhythmic medications should be considered for recurrent or refractory
postoperative
AF in an
attemptbe
to maintain
sinus rhythm.
Antiarrhythmic
medications
should
considered
for recurrent or refractory
Sotalol
may
considered
for prevention
of after
AF after
cardiacsurgery,
surgery, but
but is
postoperative
AF considered
in
an be
attempt
to prevention
maintain
sinus
rhythm.
Sotalol
may
be
for
of
AF
cardiac
is
153
IIb
A
IIbA
with risk of proarrhythmia.
associated associated
with risk of
proarrhythmia.153
Biatrial pacing may be considered for prevention of AF after cardiac surgery.153
IIb
A
IIbA
Biatrial
pacing may be considered for prevention of AF after cardiac surgery.153
IIb
B
IIbB
Corticosteroids may be considered in order to reduce the incidence of AF after

157
cardiac
surgery,
but are associated
with to
risk.
Corticosteroids
may
be considered
in order
reduce the incidence of AF after
cardiac surgery, but are associated with risk.157
161
Atrial flutter is less common than AF after cardiac surgery,
but
pharmacological therapy is similar. Prevention of postoperative atrial flutter is as
161
Atrial flutter
but
is asless
common
AFoverdrive
after pacing
cardiac
surgery,useful
difficult
prevention
of AF, than
but atrial
is generally
for
pharmacological
therapy
is similar.
Prevention
of postoperative
atrial flutter is as
termination
of atrial
flutter when
epicardial electrodes
are in place.
difficult as prevention of AF, but atrial overdrive pacing is generally useful for
termination of atrial flutter when epicardial electrodes are in place.
9.2 ACUTE CORONARY SYNDROME
9.2 ACUTEAF
CORONARY
SYNDROME
occurs with an
incidence between
2 to 21% in patients with ACS162 and is
58
more commonly associated with ACS in older patients and those with higher
162
Ib B

IIb A
Sotalol may be considered for prevention of AF after cardiac surgery, but is

associated with risk of proarrhythmia.153
Atrial flutter is less common than AF after cardiac surgery,161 but

pharmacological
is similar.
Prevention
of postoperative
atrial flutter
is153as
Biatrialtherapy
pacing may
be considered
for prevention
of AF after cardiac
surgery.
IIb A
Corticosteroids
be epicardial
considered electrodes
in order to reduce
the incidence of AF after
termination
of atrial fluttermay
when
are in place.
IIb B
Atrial
flutter
is
less
common
than
AF
after
cardiac
surgery,161
but
9.2 ACUTEpharmacological
CORONARY SYNDROME
therapy is similar. Prevention of postoperative atrial flutter is as
termination of atrial flutter when epicardial electrodes are in place.
AF occurs with an incidence between 2 to 21% in patients with ACS162 and is

more commonly associated with ACS in older patients and those with higher
162 SYNDROME
9.2 LV
ACUTE
CORONARY
dysfunction.
heart rate and
AF is associated with increased in-hospital mortality in the setting of ACS.162Stroke

and is
AF occurs with an incidence between 2 to 21% in patients with ACS
rates are also
increased
in associated
patients with
AF. patients and those with higher
more
commonly
withACS
ACSand
in older
heart rate and LV dysfunction.162
Specific recommendations for management of patients with AF in the setting of

AF is primarily
associatedon
with
increased in-hospital
in the setting
ACS.tested
Stroke
becausemortality
no adequate
trials ofhave
ACS are based
consensus,
rates are also increased in patients with ACS and AF.
alternative strategies.
Specific recommendations for management of patients with AF in the setting of
Direct-current
cardioversion is recommended for patients with severe
ACS are based primarily on consensus, because no adequate trials have tested
hemodynamic
compromise
Keypoints alternative
strategies.or intractable ischemia, or when adequate rate
control cannot be achieved with pharmacological agents in patients with ACS
Direct-current cardioversion is recommended for patients with severe
and
AF.
IC
IC
hemodynamic compromise or intractable ischemia, or when adequate rate
be achieved with pharmacological agents in patients with ACS

Intravenouscontrol
beta cannot
blockers
and nondihydropyridine calcium antagonists are
and AF.
recommended to slow a rapid ventricular response to AF in patients with ACS
who do not Intravenous
have LV dysfunction,
bronchospasm,
or AV block.
beta blockers
and nondihydropyridine
calcium antagonists are
IC
IC
recommended to slow a rapid ventricular response to AF in patients with ACS
IC
IC
Intravenous amiodarone is recommended to slow a rapid ventricular response to

AF and improve LV function in patients with ACS.
do not haveisLV
dysfunction, bronchospasm,
or AVventricular
block.
Intravenouswho
amiodarone
recommended
to slow a rapid
response to
AF and improve LV function in patients with ACS.
Ia C
Intravenous administration of non-dihydropyridine calcium antagonists

(verapamil, Intravenous
diltiazem) should
be considered
to slow a rapid ventricular
response
administration
of non-dihydropyridine
calcium antagonists
C in patients
IIaC
toIIa
AF
with ACS
and should
no clinical
signs of heart
(verapamil,
diltiazem)
be considered
to slowfailure.
a rapid ventricular response
Ib C
Intravenous administration of digoxin may be considered to slow a rapid

Intravenousin administration
of digoxin
may
be considered
to slow
a rapid
ventricular
response
patients with ACS
and AF
associated
with heart
failure.
IIb
C
IIbC
III B
to AF in patients with ACS and no clinical signs of heart failure.
ventricular response in patients with ACS and AF associated with heart failure.
Administration
of ecainide
or propafenone
is notisrecommended
in in
patients
Administration
of ecainide
or propafenone
not recommended
patientswith
with
III
B
IIIB
AF in the
of ACS.163
AF in the setting
of setting
ACS.163
9.3 WOLFF-PARKINSON-WHITE (WPW) PRE-EXCITATION SYNDROMES
9.3 WOLFF-PARKINSON-WHITE (WPW) PRE-EXCITATION SYNDROMES
Since accessory pathways (AP) lack the decremental conduction properties of
the AV pathways
node, patients
AF are atproperties
risk of rapid
Since accessory
(AP)with
lackovert
the pre-excitation
decrementaland
conduction
of
conduction
across
theovert
AP, resulting
in fast ventricular
the AV node,
patients
with
pre-excitation
and AFrates
areand
at possible
risk ofsudden
rapid
(SCD)
because
degeneration
ventricular
brillation.
This
conductioncardiac
acrossdeath
the AP,
resulting
in of
fast
ventricularinto
rates
and possible
sudden
makes AF in this patient cohort a potentially life-threatening arrhythmia. For
cardiac death
(SCD) because of degeneration into ventricular brillation. This
information relating to acute and long-term pharmacological rate control in
makes AF patients
in thiswith
patient
a potentially
arrhythmia. For
an AP,cohort
see Section
5.1.1, pagelife-threatening
18.
patients with
an SUDDEN
AP, see DEATH
SectionAND
5.1.1,
page
18.
9.3.1
RISK
STRATIFICATION
The incidence
SCDRISK
in patients
with the Wolff Parkinson White syndrome
9.3.1 SUDDEN
DEATH of
AND
STRATIFICATION
has ranged from 0.15 to 0.39% over 3- to 22-year follow-up.
The incidence
of SCDofinincreased
patientsrisk
with
The markers
are:the Wolff Parkinson White syndrome
has ranged from
0.15 topre-excited
0.39% over
to 22-year
x Shortest
RR3-interval
<250 follow-up.
ms during spontaneous or induced
AF.
The markers of
increased
risk are: tachycardia.
xA
history of symptomatic
The presenceRR
of multiple
x Shortest xpre-excited
intervalAPs.
<250 ms during spontaneous or induced
59
x Ebsteins anomaly.
AF.
x A history of symptomatic tachycardia.
Since accessory pathways (AP) lack the decremental conduction properties of

the AV node, patients with overt pre-excitation and AF are at risk of rapid
conduction across the AP, resulting in fast ventricular rates and possible sudden
cardiac death (SCD) because of degeneration into ventricular brillation. This
makes AF in this patient cohort a potentially life-threatening arrhythmia. For
patients with an AP, see Section 5.1.1, page 18.
9.3.1 SUDDEN DEATH AND RISK STRATIFICATION
The incidence of SCD in patients with the Wolff Parkinson White syndrome
has ranged from 0.15 to 0.39% over 3- to 22-year follow-up.
The markers of increased risk are:
x Shortest pre-excited RR interval <250 ms during spontaneous or induced
AF.
x A history of symptomatic tachycardia.
x The presence of multiple APs.
x Ebsteins anomaly.
Since the efficacy of catheter ablation of APs is 95%, this is the management of
choice for patients with evidence pre-excitation and AF.16 Patients who have
survived SCD in the presence of an overt AP should have urgent AP ablation.
Successful catheter ablation in those patients eliminates the risk for SCD.
Patients with overt pre-excitation and high risk of AF, or patients with high-risk
professions such as public transport vehicle drivers, pilots, or competitive
athletes should be considered for ablation.
The indication for catheter ablation of an overt AP in an asymptomatic patient is
still controversial (especially in children).165 Most patients with asymptomatic preexcitation have a good prognosis; SCD is rarely the rst manifestation of the
disease.
The positive predictive value of invasive electrophysiological testing is
considered to be too low to justify routine use in asymptomatic patients. Catheter
ablation of an asymptomatic overt AP should remain a case-by-case decision
with detailed counseling of the patient (and family) about the natural course and
the risk of SCD versus the risk of an ablation procedure.
Catheter
ablation of an overt AP in patients with AF is recommended to prevent
Keypoints
SCD.164
IA
IA
Catheter ablation of an overt AP in patients with AF is recommended to prevent

164
Immediate SCD.
referral to an experienced ablation centre for catheter ablation is
recommended
for patients
SCD
and have
of ablation
overt AP
Immediate
referral who
to ansurvived
experienced
ablation
centreevidence
for catheter
is
I CIC
conduction.
recommended for patients who survived SCD and have evidence of overt AP
conduction.
Catheter ablation is recommended for patients with high-risk professions (e.g.

Catheter
ablation
is recommended
forasymptomatic
patients with high-risk
professions
pilots,
public
transport
drivers)
and overt but
AP conduction
on(e.g.
the
I BIB
164 public transport drivers) and overt but asymptomatic AP conduction on the
pilots,
surface ECG.
164
surface ECG.
Catheter ablation
recommended
in patients
at high
risk risk
of developing
Catheterisablation
is recommended
in patients
at high
of developingAF
AFininthe
the
166
I BIB
presence
ofpresence
an overtofbut
asymptomatic
AP onAP
theonsurface
ECG.
an overt
but asymptomatic
the surface
ECG.166
Asymptomatic
patients
with evidence
an overt
AP should
considered for
for
IIa
B
Asymptomatic
patients with
evidence
of an of
overt
AP should
be be
considered
IIaB
166
catheter
the AP
only
a full explanation
careful
counseling.166
catheter ablation
ofablation
the APofonly
after
a after
full explanation
andand
careful
counseling.
9.4 HYPERTHYROIDISM
9.4 HYPERTHYROIDISM
AF occurs in 10% to 25% of patients with hyperthyroidism, more commonly in
and elderly
patients.
AF occurs men
in 10%
to 25%
of patients with hyperthyroidism, more commonly in
men and elderly patients.
Treatment is directed primarily toward restoring a euthyroid state, which is usually
associated with a spontaneous reversion to sinus rhythm.

Treatment is
directed primarily toward restoring
a euthyroid state, which is usually
60
associated Antiarrhythmic
with a spontaneous
reversion
to sinus
rhythm. are generally unsuccessful
drugs and
direct-current
cardioversion
Ia B
164
surface
ECG. with evidence of an overt AP should be considered for
Asymptomatic
patients
catheter ablation of the AP only after a full explanation and careful counseling.166
IB
Catheter ablation is recommended in patients at high risk of developing AF in the

presence of an overt but asymptomatic AP on the surface ECG.166
IIa B
Asymptomatic patients with evidence of an overt AP should be considered for
9.4 HYPERTHYROIDISM
of the
AP only after
explanation and careful
AF occurs catheter
in 10%ablation
to 25%
of patients
witha full
hyperthyroidism,
more counseling.
commonly166in
men and elderly patients.
9.4 HYPERTHYROIDISM
Treatment is directed primarily toward restoring a euthyroid state, which is usually

AF occurs in 10% to 25% of patients with hyperthyroidism, more commonly in
associated men
withand
a spontaneous
reversion to sinus rhythm.
elderly patients.
Antiarrhythmic
drugsisand
direct-current
cardioversion
are generally
unsuccessful
Treatment
directed
primarily toward
restoring a euthyroid
state, which
is usually
associated withpersists.
a spontaneous reversion to sinus rhythm.
while the thyrotoxicosis
Antiarrhythmic
drugs and direct-current
are generally
unsuccessful
The occurrence
of hyperthyroidism
following cardioversion
treatment with
amiodarone
is often
while the thyrotoxicosis persists.
encountered
in clinical practice. There are two types of amiodarone-induced
hyperthyroidism:
The occurrence of hyperthyroidism following treatment with amiodarone is often
encountered
in clinical
practice.
There are two production
types of amiodarone-induced
x Type I,
where there
is an excess
iodide-induced
of T4 and T3
x Type hyperthyroidism:
II, where there is a destructive thyroiditis with a transient excess
x Type
I, where
there later,
is an excess
iodide-induced
production of T4 and T3
release of
T4 and
T3, and,
reduced
thyroid function.
x Type II, where there is a destructive thyroiditis with a transient excess
release of T4 and T3, and, later, reduced thyroid function.
Although amiodarone may be continued when hypothyroidism has been

successfully
treatedamiodarone
with replacement
is necessary
to discontinue
Although
may be therapy,
continued itwhen
hypothyroidism
has been
amiodaronesuccessfully
if hyperthyroidism
Thyrotoxicosis
may alsoto occur
after
treated withdevelops.
replacement
therapy, it is necessary
discontinue
amiodarone
if
hyperthyroidism
develops.
Thyrotoxicosis
may
also
occur
after
cessation of amiodarone therapy.
cessation of amiodarone therapy.
IC
C
II C
IC
IC
Keypoints
In patients Inwith
active
disease,
antithrombotic
therapy
patients
withthyroid
active thyroid
disease,
antithrombotic
therapyis isrecommended
recommended
IIC
C on the presence of other stroke risk factors.
based
based on the presence of other stroke risk factors.
Administration
of a -blocker
is recommended
to control
the
rateofofventricular
ventricular
Administration
of a -blocker
recommended
to control
rate
When
a -blocker
cannot
beis used,
administration
of athenon-dihydropyridine
IIC
C
inwith
patients
with
AF complicating
thyrotoxicosis,
unless
contraindicated.
responsechannel
inresponse
patients
AF (diltiazem
complicating
thyrotoxicosis,
unless
contraindicated.
calcium
antagonist
or verapamil)
is recommended
to control
the ventricular
ratea in-blocker
patientscannot
with AF
thyrotoxicosis.
When
beand
used,
administration of a non-dihydropyridine
IC
IC
calcium channel antagonist (diltiazem or verapamil) is recommended to control
ventricular
rate in patients
with AF itand
If a rhythmthe
control
strategy
is desirable,
is thyrotoxicosis.
necessary to normalize thyroid
When
a -blocker cannot
be used,the
administration
of aremains
non-dihydropyridine
function
prior
to cardioversion,
as otherwise
risk of relapse
high.
IC
Ifcalcium
a rhythm
control
strategy
is
desirable,
it
is necessary
to normalize
channel antagonist (diltiazem or verapamil)
is recommended
to thyroid
control
IC
IC
function
prior torate
cardioversion,
as otherwise
the risk of relapse remains high.
the ventricular
in patients with
AF and thyrotoxicosis.
Once a euthyroid state is restored, recommendations for antithrombotic
prophylaxis
the
as for
patients
without recommendations
hyperthyroidism.
Once
a same
euthyroid
state
is isrestored,
antithrombotic
IC
IC
Ifare
a rhythm
control
strategy
desirable,
it is necessary tofor
normalize
thyroid
IC
prophylaxis
are
same as foras
patients
without
hyperthyroidism.
function prior
to the
cardioversion,
otherwise
the risk
of relapse remains high.
Once a euthyroid state is restored, recommendations for antithrombotic

9.5.I CPREGNANCY
9.5.
PREGNANCY
prophylaxis
are the same as for patients without hyperthyroidism.
AF is rare AF
during
pregnancy
and usually
has an
underlying
is rare
during pregnancy
and usually
hasidentifiable
an identifiable
underlying cause,
cause,
such as: such
as:
9.5. PREGNANCY
167
167
ois Mitral
stenosis,
o MitralAF
stenosis,
rare during
pregnancy and usually has an identifiable underlying cause,
168
such
o as:
congenital heart disease,
or
168
o congenital heart disease,
169
167
o hyperthyroidism.
or
o Mitral stenosis,
169
o hyperthyroidism.
A o
rapid
ventricular
response168 or
to AF
congenital
heart disease,
can
have
serious
hemodynamic
A rapid ventricular
AF and
can
serious
hemodynamic
consequencesresponse
for both169
the to
mother
the have
foetus. In
a pregnant
woman who
oforhyperthyroidism.
develops
AF, diagnosis
and and
treatment
of the underlying
condition
causingwho
the
consequences
both
the mother
the foetus.
In a pregnant
woman
arrhythmia
the
firsttreatment
priorities.
A diagnosis
rapid are
ventricular
response oftothe
AFunderlying
can have condition
serious hemodynamic
develops AF,
and
causing the
consequences
for both the mother and the foetus. In a pregnant woman who
arrhythmia are
the first priorities.
Digoxin, a beta blocker, or non-dihydropyridine calcium channel antagonist is
IC
develops AF, diagnosis and treatment of the underlying condition

causing the
recommended
the ventricular rate in pregnant patients.170-172
arrhythmia are to
thecontrol
first priorities.
Keypoints
a beta blocker, or non-dihydropyridine calcium channel antagonist is
Digoxin,
170-172
recommended
to control
ventricular
rate
in pregnant
patients.
Propranolol
andthe
metoprolol
be the
beta-blockers
of channel
choice, while
atenolol
a beta
blocker,
orwould
non-dihydropyridine
calcium
antagonist
is
Digoxin,
ICIC
is contraindicated. Atenolol given in the rst trimester, but not 170-172
later, has been
recommended to control the ventricular rate in pregnant patients.
with foetal
growth
retardation.
Use ofofbeta-blockers
in atenolol
the first
Propranololassociated
and metoprolol
would
be the
beta-blockers
choice, while
trimester
is toand
be metoprolol
preferably avoided.
Propranolol
would
thetrimester,
beta-blockers
choice,
while
is contraindicated.
Atenolol
given in
the be
rst
butofnot
later,
hasatenolol
been
iswith
contraindicated.
Atenolol
given in the
rst of
trimester,
but not later,
has been
associated All
foetal available
growth
retardation.
Use
beta-blockers
in cross
the
first
currently
drugs
have
potential to
the
associated
with foetal antiarrhythmic
growth retardation.
Use
ofthe
beta-blockers
in the first
trimester is placenta
to be preferably
avoided.
and
breast
milk
and should therefore be avoided if possible.
trimester
is toenter
be preferably
avoided.
171
173
173
and flecainide
havehave
all been
used successfully
for
Quinidine,
61
All currently
antiarrhythmic
drugs drugs
have
the
potential
totocross
All available
currently sotalol,
available
antiarrhythmic
the
potential
cross the
the
pharmacological
cardioversion
during
pregnancy,
however,
relatively small
placenta
and enter
breast
and
should
therefore
be avoided
if possible.
placenta and
enter breast
milk
andmilk
should
therefore
be avoided
if in
possible.
numbers of cases.
IC
Digoxin, a beta blocker, or non-dihydropyridine calcium channel antagonist is

recommended to control the ventricular rate in pregnant patients.170-172
Propranolol and metoprolol would be the beta-blockers of choice, while atenolol
is contraindicated. Atenolol given in the rst trimester, but not later, has been
associated with foetal growth retardation. Use of beta-blockers in the first
trimester is to be preferably avoided.
All currently available antiarrhythmic drugs have the potential to cross the
placenta and enter breast milk and should therefore be avoided if possible.
Quinidine,171 sotalol,173 and flecainide173 have all been used successfully for
pharmacological cardioversion during pregnancy, however, in relatively small
numbers of cases.
DCCV can be performed safely at all stages of pregnancy, and is recommended

Quinidine (has the longest record of safety in pregnancy) or procainamide may
IIbC
inIIbC
patients who
are haemodynamically
unstable
due to AF,
whenever the
risk
be considered
for pharmacological
cardioversion
in and
hemodynamically
stable
171,174
of ongoingpatients
AF iswho
considered
the mother
or for the foetus. Foetal
develop AFhigh,
during for
pregnancy.
monitoring should be done during and following the DCCV.
DCCV can be performed safely at all stages of pregnancy, and is recommended
in patients who are haemodynamically unstable due to AF, and whenever the risk
of ongoing AF is considered high, for the mother or for the foetus. Foetal
anticoagulation
to prevent systemic arterial embolism has not been
The role ofmonitoring
should be done during and following the DCCV.
I CIC
systematically studied in pregnant patients with AF, but the arrhythmia is

frequently associated with conditions that carry a high risk of thromboembolism,
to disease.
prevent systemic arterial embolism has not been
The role oforanticoagulation
including congenital
valvular heart
systematically studied in pregnant patients with AF, but the arrhythmia is
frequentlythromboembolism
associated with conditions
that carry a high
risk of thromboembolism,
Protection against
is recommended
throughout
pregnancy for
including congenital or valvular heart disease.
patients with AF except those at low thromboembolic risk. The choice of
anticoagulant
or aspirin
should
be chosen according
to the throughout
stage of pregnancy.
Protection
against
thromboembolism
is recommended
pregnancy for
ICIC
patients with AF except those at low thromboembolic risk. The choice of
anticoagulant
be chosen warfarin
according to
the stageitof crosses
pregnancy.the
Consideration
should or
beaspirin
givenshould
to avoiding
because
placental barrier and is associated with teratogenic embryopathy in the first
172-179 the
Consideration
should
be
given
to
avoiding
warfarin
because
it
trimester and with foetal haemorrhage in the later stages of pregnancy.crosses
placental barrier and is associated with teratogenic embryopathy in the first
trimester and with foetal haemorrhage in the later stages of pregnancy. 172-179
Heparin is the preferred anticoagulant because it does not cross the placenta.
Heparin is the preferred anticoagulant because it does not cross the placenta.
Subcutaneous administration of LMWH in weight-adjusted therapeutic doses is

Subcutaneous
of and
LMWH
weight-adjusted
therapeutic doses is
recommended
during theadministration
rst trimester
theinlast
month of pregnancy.
recommended
the rst
last month
of pregnancy.
I BIB
Alternatively,
UFH may during
be given,
to trimester
prolongand
thethe
activated
partial
thromboplastin
Alternatively, UFH may
180 be given, to prolong the activated partial thromboplastin
time to 1.5 time
times
control.
to the
1.5 times
the control.180
During the
second trimester,
consider
pregnantwomen
women
During
trimester,
consider
for for
pregnant
IIbC
IIbC the second
180
with AF
at high thromboembolic
with AF at high
thromboembolic
risk.180risk.
The following are guiding principles for the use of drugs in pregnancy:
The following are

guiding principles for the use of drugs in pregnancy:
o Frequent monitoring with ECG and drug levels is recommended to reduce
o Frequent monitoring
with ECG and drug levels is recommended to reduce
the risk of toxicity.
the riskoof Iftoxicity.
possible, start after 8 weeks of pregnancy or as late as possible.
o Use
lowest
dose.
o If possible,
start
aftereffective
8 weeks
of pregnancy or as late as possible.
o Low
dose combination
therapy preferable to higher dose single drug
o Use lowest
effective
dose.
o Low dose therapy.
combination therapy preferable to higher dose single drug
o Use older agents with longest tract record.
therapy.
o Use older agents with longest tract record.
9.6 HYPERTROPHIC CARDIOMYOPATHY
Patients with hypertrophic cardiomyopathy (HCM) are at greater risk of
9.6 HYPERTROPHIC
CARDIOMYOPATHY
developing AF
compared with the general population, and around 20 25%
develop AF with an annual incidence of 2%.
Patients with hypertrophic cardiomyopathy (HCM) are at greater risk of

developing AF compared with the general population, and around 20 25%
develop AF with an annual incidence of 2%.
62
B
IB
B
IB
Ia C
IIa C
Ia C
IIa C
Ia C
IIa C
AF is the major determinant of hemodynamic deterioration in patients with HCM

AF is
the majorcan
determinant
of hemodynamic
deterioration
in patients with HCM
and
symptoms
be ameliorated
by restoration
of sinus rhythm.
and symptoms can be ameliorated by restoration of sinus rhythm.
Amiodarone may be the most effective agent for reducing the occurrence of
AmiodaroneAF
may
most effective
agent for reducing the occurrence of
paroxysmal
andbe
for the
preventing
recurrence.
paroxysmal AF and for preventing recurrence.
AF is the major determinant of hemodynamic deterioration in patients with HCM
In chronic and
AF,symptoms
rate control
can usually
be achieved
-blockers and
can be ameliorated
by restoration
of sinuswith
rhythm.
In chronicAV
AF,
rateablation
controlwith
canpermanent
usually be
achievedpacing
with (to
-blockers
and
verapamil.
nodal
ventricular
promote late
verapamil.
AV
nodal
ablation
with
permanent
ventricular
pacing
(to occurrence
promote late
Amiodarone
may
be
the
most
effective
agent
for
reducing
the
of
septal activation) may be helpful in selected patients.
paroxysmal
for preventing
recurrence.
septal activation)
mayAF
beand
helpful
in selected
patients.
Unless contraindicated, OAC therapy should be administered to patients with
In chronic AF, OAC
rate control
can
usuallybebeadministered
achieved with -blockers with
and
Unless
therapy
should
HCM
andcontraindicated,
paroxysmal,
or permanent
AF.ventricular pacingto(topatients
verapamil. AVpersistent,
nodal ablation
with permanent
promote late
HCM and paroxysmal,
persistent, or permanent AF.
septal activation) may be helpful in selected patients.
Outcomes after AF ablation in patients with HCM are favourable, but not as
Outcomes Unless
afterin AF
ablation populations.
in OAC
patients
with
HCMbeare
but
notwith
as
contraindicated,
therapy
administered
to patients
successful
as
unselected
LAshould
ablation
isfavourable,
signicantly
better
in
and
paroxysmal,
persistent,
AF.
successful HCM
as
unselected
populations.
LA ablation
is signicantly
better
in
paroxysmal
AF in
than
in persistent
AF. or
In permanent
addition,
patients
with marked
atrial
paroxysmal AF
in diastolic
persistent
AF. In addition,
patients
marked atrial
enlargement
and than
severe
dysfunction
are at high
risk ofwith
recurrence.
Outcomes
after
AF
ablation
in
patients
with
HCM
are
favourable,
but
not
as
enlargement and severe diastolic dysfunction are at high risk of recurrence.
successful as in unselected populations. LA ablation is signicantly better in
The small series
of surgical
(Maze-III
procedure)
in combination
with
paroxysmal
AF than ablation
in persistent
AF. In addition,
patients
with marked atrial
The small enlargement
series
surgical
ablation
(Maze-III
procedure)
infor
combination
with
myomectomy
whenofLV
outflow
tract
obstruction
present,
AF in patients
and
severe
diastolic
dysfunctionwas
are at
high risk
of
recurrence.
myomectomy
whenno
LVincrease
outflow tract
obstruction
was present,
for AF
in patients
with
HCM showed
in operative
mortality
and a high
proportion
of
181
The
smallin
series
of surgical
ablation
procedure)
in combination
with
with HCM
showed
no
increase
in operative
mortality
and a high
of
patients
remained
sinus
rhythm
over a(Maze-III
mean
follow-up
of
15proportion
months.
181
myomectomy
when LV
outflow over
tract obstruction
was present,offor15
AFmonths.
in patients
patients
remained
in
sinus
rhythm
a
mean
follow-up
Despite conicting data, there seems to be an overall benecial effect of
with HCM showed
no increase
in operative
mortality
a high proportion
Despite conicting
data,the
there
seems
be an
overallandbenecial
effect of
of
myomectomy
in reducing
of AFtoinover
HCM
patients.
patients
remained
inburden
sinus rhythm
a mean
follow-up of 15 months.181
myomectomy
in reducing the burden of AF in HCM patients.
Despite conicting data, there seems to be an overall benecial effect of
Restorationmyomectomy
of sinus rhythm
bytheDCCV
orAFpharmacological
in reducing
burden of
in HCM patients. cardioversion is
Keypoints
Restoration ofinsinus
rhythm
by DCCV
or pharmacological
is
recommended
patients
with HCM
presenting
with recent-onset cardioversion
AF.182
182
Restoration
of sinus
rhythmpresenting
by DCCV with
or pharmacological
cardioversion is
recommended
in patients
with HCM
recent-onset AF.
recommended in patients with HCM presenting with recent-onset AF.182
IB
IB therapy
OAC
(INR 2.03.0) is recommended in patients with HCM who develop
182is recommended in patients with HCM who develop
OAC
therapy
(INR 2.03.0)
AF
unless
contraindicated.
OAC therapy (INR182
2.03.0) is recommended in patients with HCM who develop
AF
IB
IBunless contraindicated.
AF unless contraindicated.182
Amiodarone should be considered in order to achieve rhythm control and to
Amiodarone
should
considered
order
to achieve
rhythm
to
Amiodarone
should
be considered
in order
to achieve
rhythmcontrol
control and
and to
maintain
sinus
rhythmbe
in
patients
withinHCM.
IIa
C
IIaC
maintain
sinusinrhythm
in patients
with HCM.
maintain
sinus
rhythm
patients
with HCM.
Catheter ablation of AF should be considered in patients with symptomatic AF
Catheter of
ablation
of AF should
be considered
in patients
withsymptomatic
symptomatic AF
Catheter
ablation
AF should
be considered
in patients
with
AF
IIa
C
refractory
torefractory
pharmacological
control.
IIaC
to pharmacological
control.
refractory to pharmacological control.
Ablation
procedures
(with concomitant
septalseptal
myomectomy
if indicated)
Ablation procedures
(with concomitant
myomectomy
if indicated)may
may be
be
IIa
C
IIaC
Ablation
procedures
(with
concomitant
septal
myomectomy
if indicated) may be
considered
patients
with
HCM
and
refractory
considered
in patientsin
with
HCM
and
refractory
AF. AF.
considered in patients with HCM and refractory AF.
9.7 PULMONARY DISEASES
9.7 PULMONARY
DISEASES
9.7 PULMONARY DISEASES
Supraventricular arrhythmias, including AF, are common in patients with COPD
with COPD
Supraventricular
arrhythmias,
including
AF, areincommon
in patients
and have
adverse prognostic
implications
patients with
acute exacerbations
of
with COPD
Supraventricular
including AF,
are common
in patients
and
have adverse
prognostic implications
in patients
with acute
exacerbations
of
COPD. arrhythmias,
and have adverse prognostic implications in patients with acute exacerbations of
COPD.
COPD.
Keypoints
IC
IC
For patients who develop AF during an acute pulmonary illness or exacerbation

of chronic pulmonary disease, treatment of the underlying lung disease and
correction of hypoxemia and acidosis are the primary therapeutic measures.
IIIC
IIIC
Theophylline and beta-adrenergic agonist agents are not recommended in

patients with bronchospastic lung disease who develop AF.
IIIC
IIIC
Beta-blockers, sotalol, propafenone, and adenosine are contraindicated in

patients with bronchospasm.
IC
Diltiazem or verapamil is recommended

to control the ventricular rate in patients
63
with obstructive pulmonary disease who develop AF with or without digoxin.
IC
of chronic pulmonary disease, treatment of the underlying lung disease and
patients with
bronchospastic lung disease who develop AF.
correction of hypoxemia and acidosis are the primary therapeutic measures.
Beta-blockers,
sotalol,and
propafenone,
andagonist
adenosine
contraindicated
Theophylline
beta-adrenergic
agents are
are not
recommended in
in
IIIC
patients
with bronchospastic lung disease who develop AF.
bronchospasm.
patients with
Beta-blockers,
propafenone,
and adenosine
are contraindicated
in
Diltiazem
or
verapamil issotalol,
recommended
to control
the ventricular
rate in patients
IIIC
patients with bronchospasm.
with obstructive
pulmonary disease who develop AF with or without digoxin.
Diltiazem or verapamil is recommended to control the ventricular rate in patients
ICICselective blockers (e.g. bisoprolol) in small doses should be considered as an

-1
with obstructive pulmonary disease who develop AF with or without digoxin.
alternative for ventricular rate control.
IIa
C
IIaC
-1 selective blockers (e.g. bisoprolol) in small doses should be considered as an
alternative
for ineffective
ventricular rate
control.AF unless respiratory decompensation
Cardioversion
may be
against
has been corrected.
Cardioversion may be ineffective against AF unless respiratory decompensation
has been corrected.
Direct-current cardioversion should be attempted in patients with pulmonary

disease who
become hemodynamically
unstable
as a consequence
of AF.
Direct-current
cardioversion should
be attempted
in patients with
pulmonary
ICIC
disease who become hemodynamically unstable as a consequence of AF.
In patients refractory to drug therapy, AV nodal ablation and ventricular pacing

In patients
to drug
therapy,rate.
AV nodal ablation and ventricular pacing
to refractory
control the
ventricular
may be necessary
may be necessary to control the ventricular rate.
In patientsInwith
AF and
pulmonary
disease,
the general
recommendations
patients
with AF
and pulmonary
disease,
the general
recommendations for
for
antithrombotic
therapy apply.
antithrombotic
therapy apply.
HEART FAILURE
9.8 HEART9.8
FAILURE
AF is a strong and independent risk factor for the development of heart failure,
AF is a strong
and conditions
independent
risk factor
for17,183
theThe
development
failure,
onset of AFof
in heart
a patient
with
and both
frequently
co-exist.
17,183
The onset of
AF in a topatient
with
and both conditions
co-exist.
heart failure frequently
often leads to
symptomatic deterioration,
predisposes
episodes
of
heart failure
often leads
symptomatic
deterioration,
predisposes toepisodes,
episodesand
of
worsening
hearttofailure,
increases
the risk of thrombo-embolic
long-term
outcome. the risk of thrombo-embolic episodes, and
worsening worsens
heart failure,
increases
worsens long-term outcome.
In the initial approach to heart failure patients with AF, the following issues need
to be considered:17
In the initial approach to heart failure patients with AF, the following issues need
17
to be considered:
x Potential precipitating factors and secondary causes should be identied
x
x
and if possible corrected.
Potential
factors
and
secondary
should be identied
x precipitating
Background heart
failure
treatment
shouldcauses
be optimized.
and if possible corrected.
When
ventricular
rate
control
is
required
in
patients
with
heart
Background heart failure treatment should be optimized. failure and AF, -
When ventricular rate control is required in patients with heart failure and AF, blockers are preferred over digitalis glycosides due to their rate-controlling effect
during exertion rather than only at rest. A combination of digoxin and a -blocker
may be more effective than a single drug for heart-rate control at rest. Therapy
with -blockers alone or in combination with digoxin was associated with lower
mortality rates compared with treatment with digoxin alone.184
-Blockers have favourable effects on mortality and morbidity in patients with
systolic heart failure. A recent meta-analysis also showed a 27% reduction in the
incidence of new-onset AF in patients with systolic heart failure treated with blockers.185
Although diltiazem effectively controls excessive heart rate during exercise, it
adversely suppresses myocardial contraction and increases the risk of heart
failure. For patients with heart failure and preserved ejection fraction, these drugs
used in combination with digoxin appear to be more effective in controlling heart
rate over 24 h and during exercise than digoxin or non-dihydropyridine calcium
channel antagonist monotherapy.
The rhythm control strategy has not been shown to be superior to rate control in
heart failure patients with AF.27 Catheter-based LA ablation procedures in heart
failure patients may lead to improvement in LV function, exercise tolerance, and
quality of life in selected patients (see Section 8.3.1).29,30
64
The prevention of thrombo-embolism is covered in Section 6, but the presence of
heart failure due to systolic dysfunction is itself a risk factor for stroke and
Although
effectively than
controls
excessive
heart rate during exercise,
it
rate over 24
h anddiltiazem
during exercise
digoxin
or non-dihydropyridine
calcium
adversely monotherapy.
suppresses myocardial contraction and increases the risk of heart
channel antagonist
failure. For patients with heart failure and preserved ejection fraction, these drugs
used in combination with digoxin appear to be more effective in controlling heart
The rhythmrate
control
strategy
has not
been than
shown
to be
to rate control
in
over 24
h and during
exercise
digoxin
or superior
non-dihydropyridine
calcium
27
Catheter-based LA ablation procedures in heart
heart failure
patients
with AF.
channel
antagonist
monotherapy.
Theinrhythm
control
strategy
hasSection
not been8.3.1).
shown29,30
to be superior to rate control in
quality of life
selected
patients
(see
27
heart failure patients with AF.
Catheter-based LA ablation procedures in heart

The prevention
of thrombo-embolism is covered in Section 6, but the presence of
quality of life in selected patients (see Section 8.3.1).29,30
thrombo-embolism,
and of
OAC
therapy is generally
indicated
when
present.of
The prevention
thrombo-embolism
is covered
in Section
6, butAF
theispresence
and OAC therapy

is generally
indicated when
present. in
The use ofthrombo-embolism,
aspirin is not recommended
due
to the increased
risk AF
of is
bleeding
combination with OAC therapy and some evidence that aspirin may increase the
The use of aspirin is not recommended due to the increased risk of bleeding in
risk of hospitalizations
for heart failure.
combination with OAC therapy and some evidence that aspirin may increase the
risk of hospitalizations for heart failure.
IC
Keypoints
DCCV is recommended when a rapid ventricular rate does not respond to
DCCV ismeasures
recommended
a rapid
rate ongoing
does not myocardial
respond to
pharmacological
in when
patients
withventricular
AF and
I CIC
measures inorpatients
withofAF
and ongoing
myocardial
ischaemia,pharmacological
symptomatic hypotension,
symptoms
pulmonary
congestion.
IC
In patientsInwith
AF with
and AF
severe
(NYHA(NYHA
classclass
III or
or orrecent
patients
and severe
III IV)
or IV)
recent (<4
(<4 weeks)
weeks)
unstable
heart
failure,
use the
of antiarrhythmic
therapy
to maintain
I CIC
unstable
heartthe
failure,
use of antiarrhythmic
therapy
to maintainsinus
sinus rhythm
rhythm
should be restricted
to amiodarone.
should be restricted
to amiodarone.
IIa B
IIa C
IIb B
IIb B
ischaemia, symptomatic hypotension, or symptoms of pulmonary congestion.
of amiodarone
a reasonable
optionforforpharmacological
pharmacological
Administration
of amiodarone
is a isreasonable
option
Administration
21,39,45,186
IIa
B
IIaB
cardioversion of AF, or to facilitate electrical cardioversion of AF.
cardioversion
of AF, or to facilitate electrical cardioversion of AF.21,39,45,186
In patients with AF and stable heart failure (NYHA class I, II) dronedarone should
C
IIaC
InIIa
patients
with
AF and to
stable
heart
failure (NYHA
class I, II) dronedarone should
be
considered
reduce
cardiovascular
hospitalizations.
For patients
with
heart failure
and
symptomatic
persistent AF despite adequate
be considered to reduce cardiovascular hospitalizations.
rate control,
electrical
cardioversion
and rhythm
be
For patients
with heart
failure and symptomatic
persistent control
AF despitemay
adequate
27,29,30,32,187
IIb
B
IIbB
rate
control, electrical cardioversion and rhythm control may be
considered.
27,29,30,32,187
considered.
Catheter ablation (pulmonary vein isolation) may be considered in heart failure

Catheter ablation (pulmonary vein29,30
isolation) may be considered in heart failure
IIb
B
patients
with
refractory
symptomatic
AF. AF.29,30
IIbB
patients
with refractory
symptomatic
9.9 ATHLETES
9.9 ATHLETES
In population-based studies, the intensity of physical activity showed a U-shaped
In population-based
studies, the intensity of physical activity showed a U-shaped
relationship with incident AF, which may indicate that the positive antiarrhythmic
relationshipeffects
with incident
AF, which
the positive
antiarrhythmic
of physical
activity may
are indicate
partially that
negated
when exercise
is too
effects of strenuous.
physical188,189
activity
partially
negated in when
is too
AF is 2 are
10 times
more prevalent
active orexercise
former competitive
188,189
190,191
AFand
is 2those
10performing
times more
prevalent
in active
or former
competitive
strenuous. athletes
The
intense
recreational
endurance
sports.
190,191
reasons
this association
are probably
both functional
(increased
The
athletes and
thoseforperforming
intense
recreational
endurance
sports.sympathetic
volume loadare
during
exercise,
at rest)
and structural
(atrial
reasons foractivity,
this association
probably
bothvagotonia
functional
(increased
sympathetic
hypertrophy and dilatation).
activity, volume load during exercise, vagotonia at rest) and structural (atrial
hypertrophyRate
andcontrol
dilatation).
is difficult to achieve in athletes. -blockers are not well tolerated
and may even be prohibited in some competitive sports, and digoxin or non-
Rate control
is difficult tocalcium
achieve
in athletes.
are not
well heart
tolerated
dihydropyridine
antagonists
will not-blockers
be potent enough
to slow
rate
duringbe
exertional
AF. in some competitive sports, and digoxin or nonand may even
prohibited
dihydropyridine calcium antagonists will not be potent enough to slow heart rate
When the heart rate during AF is acceptable at maximal physical performance for
during exertional
AF.
a given athlete without signs of haemodynamic impairment (dizziness, syncope,
sudden fatigue), competitive sports activity can be resumed.
When the heart rate during AF is acceptable at maximal physical performance for
a given athlete
without
signs when
of haemodynamic
(dizziness,
syncope,
Caution
is necessary
using flecainide impairment
and propafenone
as monotherapy
in
maycan
leadbe
to resumed.
atrial utter, with 1 to 1 conduction
athletes
with AF.192 These
sudden fatigue),
competitive
sportsdrugs
activity
to the ventricles during high sympathetic tone. Therefore, ablation of the utter
circuit may be needed in athletes with documented atrial utter. Continuation of

Caution is necessary
when using flecainide and propafenone as monotherapy in
drug therapy
for AF will often be required despite successful ablation (hybrid
athletes with
AF.192 These drugs may lead to atrial utter, with 1 to 1 conduction
therapy).
circuit mayInbesome
needed
in with
athletes
with documented
utter. Continuation
of
athletes
paroxysmal
AF, ecainide atrial
or propafenone
can be used for
These
acute
(the pill-in-the-pocket
approach;
see Sectionablation
5.1.2.1).42(hybrid
drug therapy
forconversion
AF will often
be required despite
successful
therapy). patients should refrain from sports as long as the atrial arrhythmia persists and
until one to two half-lives of the antiarrhythmic drug have elapsed.
65
193 for
In some athletes
with paroxysmal
AF,such
ecainide
or ablation
propafenone
be used
Non- pharmacological
options
as catheter
can be can
considered.
acute conversion (the pill-in-the-pocket approach; see Section 5.1.2.1).42 These
Caution is necessary when using flecainide and propafenone as monotherapy in

athletes with AF.192 These drugs may lead to atrial utter, with 1 to 1 conduction
circuit may be needed in athletes with documented atrial utter. Continuation of
drug therapy for AF will often be required despite successful ablation (hybrid
therapy).
In some athletes with paroxysmal AF, ecainide or propafenone can be used for
acute conversion (the pill-in-the-pocket approach; see Section 5.1.2.1).42 These
patients should refrain from sports as long as the atrial arrhythmia persists and
until one to two half-lives of the antiarrhythmic drug have elapsed.
Non- pharmacological options such as catheter ablation can be considered. 193
Anticoagulation may be necessary depending on the presence of risk factors for
thrombo-embolic events (see Section 6.1). However, anticoagulation cannot be
used in individuals participating in sporting activities with a risk of bodily collision.
When a pill-in-the-pocket approach with sodium channel blockers is used, sport
cessation
Keypointsshould be considered for as long as the arrhythmia persists, and until
12 half-lives of the antiarrhythmic drug used have elapsed.
IIa
C
IIaC
When a pill-in-the-pocket approach with sodium channel blockers is used, sport
cessation
should
consideredinforcompetitive
as long as the
persists,
andwith
until
Isthmus ablation
should
bebe
considered
or arrhythmia
leisure-time
athletes
documented atrial utter, especially when therapy with ecainide or propafenone
is intended.Isthmus ablation should be considered in competitive or leisure-time athletes with
IIa
C
IIaC
IIa C
documented
atrial utter, especially
therapychannel
with ecainide
When a pill-in-the-pocket
approachwhen
with sodium
blockersorispropafenone
used, sport
IIa
C
IIaC
Where appropriate, AF ablation should be considered to prevent recurrent AF in
IIa C
ablation
should
be cause.
considered to prevent recurrent AF in
orWhere
leisureappropriate,
time sportsAF
until
correction
of the
iscessation
intended.
Where appropriate,
AF
ablation
should be
prevent recurrent
AFuntil
in
should
be considered
for considered
as long as thetoarrhythmia
persists, and
athletes.
Isthmus ablation should be considered in competitive or leisure-time athletes with

athletes.
IIa C a specic
When
cause for AF is identied in an athlete (such as
documented atrial utter, especially when therapy with ecainide or propafenone
hyperthyroidism),
ita isspecic
not recommended
to continue
participation
in competitive
is intended.
When
cause for AF
is identied
in an athlete
(such as
III
C
or IIIC
leisure time
sports until correction
of the cause.
hyperthyroidism),
it is not recommended
to continue participation in competitive
athletes.
It is not recommended
to allow physical sports activity when symptoms due to
It is not
recommended
allow
physical are
sports
activity when symptoms due to
haemodynamic
impairment
(suchtoas
dizziness)
present.
III
C
IIIC
When a specic
cause(such
for as
AFdizziness)
is identied
in an athlete (such as
haemodynamic
impairment
are present.
hyperthyroidism), it is not recommended to continue participation in competitive
or leisure time sports until correction of the cause.
9.10 VALVULAR
HEART DISEASE
9.10 VALVULAR
HEART DISEASE
It is not recommended to allow physical sports activity when symptoms due to
III C
haemodynamic
impairment
(such
as dizziness)
are
present.
AF frequently
accompanies
valvular
heart
disease.
LA distension
early
AF frequently
accompanies
valvular
heart
disease.
LA
distension
is isananearly
manifestation
of progressive
disease,
presence of
of
manifestation
of progressive
mitral mitral
valve valve
disease,
andand
thethepresence
paroxysmal
or
permanent
AF
is
an
accepted
indication
for
early
percutaneous
or
paroxysmal or
permanent
AF
is anDISEASE
accepted indication for early percutaneous or
66
9.10
VALVULAR
HEART
AF is also frequently seen in later stages of aortic
surgical mitral intervention.
surgical mitral
intervention.66 AF is also
frequently seen in later stages of aortic
valve disease when LV dilatation and elevated end-diastolic pressure exert
valve disease
when
LV
dilatation
and
elevated
end-diastolic
pressure
AF
frequently
accompanies
valvular
heart disease.
LA distension
is anexert
early
secondary effects on LA function.
manifestation
of progressive mitral valve disease, and the presence of
secondary effects
on LA function.
paroxysmal orofpermanent
AF conventional
is an acceptedrecommendations
indication for earlyinpercutaneous
Management
AF follows
the setting or
of
66
AF isaalso
in later
stages of
aortic
surgical heart
mitral disease,
intervention.
valvular
although
ratefrequently
control seen
strategy
usually
adopted
Management
of AF
follows
conventional
recommendations
inis the
setting
of
valve
disease
when
LV
dilatation
and
elevated
end-diastolic
pressure
exert
because
of the low
likelihoodaofrate
maintaining
rhythm in
long term.
valvular heart
disease,
although
controlsinus
strategy
is the
usually
adopted
secondary
effects
on LA function.
III C
because of the low likelihood of maintaining sinus rhythm in the long term.
Principal concerns surround the high risk of thrombo-embolism in subjects with

Management of AF follows conventional recommendations in the setting of
valvular heart disease, and a low threshold for anticoagulation is recommended
valvular surround
heart disease,
although a rate control strategy is usually adopted
Principal concerns
(See Section
6.1). the high risk of thrombo-embolism in subjects with
of the
lowa likelihood
of maintaining
sinus rhythm inisthe
long term.
valvular heartbecause
disease,
and
low threshold
for anticoagulation
recommended
(See SectionPrincipal
6.1). concerns surround the high risk of thrombo-embolism in subjects with
IC
OAC therapy (INR 2.03.0) is indicated in patients with mitral stenosis and AF
valvular heartpersistent,
disease, and
a low threshold for anticoagulation is recommended
(paroxysmal,
or permanent).
(See Section 6.1).
Keypoints
OAC
therapy (INR 2.03.0) is indicated in patients with mitral stenosis and AF
OAC therapy (INR 2.03.0) is recommended in patients with AF and clinically
IC
(paroxysmal,
persistent,
permanent).
signicant
mitralorregurgitation.
I CIC
(paroxysmal, persistent, or permanent).
OAC therapy
(INR 2.03.0)
recommended
in patients
with AFforand
clinically
Percutaneous
mitral is
balloon
valvotomy should
be considered
asymptomatic
IIa C
patients
with moderate
or severe
mitral stenosisinand
suitable
valve
who
signicant
mitral
OAC regurgitation.
therapy
(INR 2.03.0)
is recommended
patients
with
AF anatomy
and clinically
I CIC
have
new-onset
in the absence of LA thrombus.
signicant
mitralAF
regurgitation.
Percutaneous mitral balloon valvotomy should be considered for asymptomatic

balloon
valvotomy
should
be considered
asymptomatic
patients
withPercutaneous
moderate ormitral
severe
mitral
stenosis
and suitable
valveforanatomy
who
IIa C
patients with moderate or severe66
mitral stenosis and suitable valve anatomy who
have new-onset
AF
in
the
absence
of
LA
thrombus.
have new-onset AF in the absence of LA thrombus.
valvular heart disease, and a low threshold for anticoagulation is recommended

(See Section 6.1).
IC
(paroxysmal, persistent, or permanent).
IC
OAC therapy (INR 2.03.0) is recommended in patients with AF and clinically

signicant mitral regurgitation.
IIaC
IIa
C
IIa
C
IIaC
Percutaneous mitral balloon valvotomy should be considered for asymptomatic

patients with moderate or severe mitral stenosis and suitable valve anatomy who
have new-onset AF in the absence of LA thrombus.
Early mitral valve surgery should be considered in severe mitral regurgitation,

preserved LV function, and new-onset AF, even in the absence of symptoms,
particularly when valve repair is feasible.
10. REFERRALS
10.1 Acute hospitalisation/referral
This is required for patients with:
x AF/AFL with haemodynamic compromise, acute dyspnoea, acute heart
failure, chest pain, ischaemia, near syncope, hypotension
x AF/AFL with rapid uncontrolled heart rate, e.g., over 140 bpm at rest
x AF/AFL with acute systemic illness requiring acute management
x rst/new onset of AF/AFL symptoms, no contraindications to cardioversion,
with the possibility of cardioversion within 48 hours of onset.
10.2 Outpatient specialist physician/cardiologist
Outpatient specialist referral is recommended for those who:
x Need further investigation/echocardiography
x Have suspected structural heart disease (e.g., hypertensive, valvular,
ischaemic)
x Are to be considered for cardioversion
x Are highly symptomatic, requiring maintenance of sinus rhythm
antiarrhythmic therapy
x Are having difficulty with pharmacological rate control
x Require a second opinion of the risk/benet ratio of anticoagulation
x Are having syncopal attacks.
10.3 Cardiac electrophysiologist (heart-rhythm specialist)
Tertiary referral is recommended for patients who have:
x AF with WPW syndrome (pre-excited AF)
x Highly-symptomatic AF unresponsive to rst-line antiarrhythmic treatment
x Uncontrolled ventricular rate with maximally tolerated atrioventricularblocking therapy
x Recurrent AFL (including mixed AFL and AF where AFL is the dominant
arrhythmia)
x Tachycardia-bradycardia syndrome (sinus node dysfunction)
x Suspicion or documentation of a regular tachycardia triggering AF (e.g.,
SVT).
10.4 No referral
Referral is not needed for patients who have rate-controlled AF with mild or
occasional symptoms, for whom echocardiography is not required (e.g.,
previously obtained), and for whom the decision regarding stroke prevention
management is clear cut.
67
11. AUDIT & EVALUATION

The Table below lists the audit criteria identified to evaluate the impact of the
implementation of the six key priority areas detailed above on clinical practice
and health outcomes.
Criterion
All people presenting to
primary or secondary
care with a history of
hypertension, heart
failure, diabetes or stroke
and noted to have an
irregular pulse to be
offered an ECG and any
new diagnosis of AF
recorded.
Exception
None.
Definition of terms
Percentage of patient
records with a new
diagnosis of AF made
following an ECG made
on the basis of detection
of an irregular pulse.
All patients should be

assessed for risk of
stroke/ thromboembolism
and given
thromboprophylaxis
according to the stroke
risk stratification
algorithms and have this
assessment and any
recorded.
All patients should be
assessed for risk of
bleeding and according
to the bleeding risk
stratification algorithms
and have this
assessment recorded.
All AF patients in whom a
rate-control or rhythmcontrol strategy is
initiated to have their
involvement in choosing
a treatment strategy
recorded.
All patients who are
prescribed digoxin as
initial monotherapy for
Haemodynamically
unstable patients or
those in whom
assessment is impossible
or inappropriate.
records with a
documentation of risk
assessment and
thromboprophylaxis
consistent with the stroke
risk stratification
algorithm.
Haemodynamically
unstable patients or
those in whom
assessment is impossible
or inappropriate.
records with a
documentation of risk
assessment for bleeding
consistent with the
bleeding risk stratification
algorithm.
records with a
documentation of
involvement of the patient
in the decisionmaking
process.
Postoperative or
haemodynamically
unstable patients, or
those otherwise not able
to engage in a decisionmaking process.
None.
records with a
prescription of digoxin for
68
rate control to have the

reason for this
prescription recorded
where it is not obvious
(e.g. sedentary patient,
presence of
contraindication to
alternative agents).
All patients who are

prescribed amiodarone
as long-term therapy for
rhythm control to have
the reason for this
prescription recorded
where it is not obvious
(e.g. failure of other
agents to control rhythm,
presence of
contraindication to
alternative agents).
initial rate-control
monotherapy where the
reason for digoxin
prescription is:
Sedentary patient
Presence of contraindications to betablockers
or rate-limiting calcium
Antagonists
Other reasons.
None.
records with a
prescription of
amiodarone for long-term
rhythm-control therapy
where the reason for
amiodarone prescription
is:
Presence of contraindications to betablockers, dronedarone,
flecainide or propafenone
Other reasons.
69
APPENDIX A
Search Terms
Scope of search
A literature search was conducted for guidelines, systematic reviews and
randomized controlled trials on the primary care management of Atrial
fibrillation, with additional searches in the following areas:

Outpatient therapy
Rhythm versus rate control
Anti-arrhythmics for cardioversion
Drugs for rate control
Anticoagulation versus antiplatelet drugs to prevent thromboembolism
Stroke risk versus bleeding risk
Invasive or emerging therapies
Referral criteria
Search dates
January 2010 December 2011
Key search terms
Various combinations of searches were carried out. The terms listed below are
the core search terms that were used for Medline and these were adapted for
other databases.

exp Atrial Fibrillation/, atrial fibrillation.tw

exp Diagnosis/, exp Diagnosis, Differential/, exp Electrocardiography/,
exp Echocardiography/, exp Radiography, Thoracic/, exp Thyroid
Function Tests/, exp Hematologic Tests/, blood test$.tw
exp atrial flutter.tw
Outpatients/
Ambulatory Care/
(outpatient or out-patient).tw.
exp Platelet Aggregation Inhibitors/, exp Aspirin/, exp Warfarin/
exp thromboembolism/
exp anticoagulants/
$thromb$.ti,ab.
anticoagul$.tw.
exp Blood Coagulation/de, dt, pc [Drug Effects, Drug Therapy,
Prevention & Contro
exp Platelet Aggregation Inhibitors/
Aspirin/
aspirin.tw.
exp Anti-Arrhythmia Agents/, exp Calcium Channel Blockers/, exp
Verapamil/, exp Diltiazem/, exp Nifedipine/
exp Adrenergic beta-Antagonists/, exp Atenolol/, exp Bisoprolol/,
exp Metoprolol/, exp Acebutolol/, exp Nadolol/, exp Oxprenolol/, exp
Propranolol/
70
exp Digoxin/, exp Amiodarone/

cardioversion/
defibrillation/
(countershock$ or (counter adj shock$)).tw. cardioconver$.tw.
(electr$ adj3 (cardiover$ or conver$ or countershock)).tw. rhythm
control.tw.
(electrover$ or (electric$ adj3 defibrillat$)).tw
(antiarrhythm$ or anti-arrhythm$).tw.
(pharmacol$ adj3 (cardiover$ or conver$ or cardioconver$)).tw.
exp heart rate/
(heart or cardiac or ventricular) adj3 rate).tw.
(rate adj3 (control$ or reduc$ or normal$)).tw.
(chronotrop$ adj3 therapy).tw.
Digoxin/
Verapamil/
Diltiazem/
(beta$ adj block$).tw.
exp Beta Adrenergic Receptor Blocking Agent/
Amiodarone/
Clonidine/
(ventricular adj5 pac$).
exp thromboembolism/
exp anticoagulants/
$thromb$.ti,ab.
anticoagul$.tw.
exp Blood Coagulation/de, dt, pc [Drug Effects, Drug Therapy,
Prevention & Control
exp Platelet Aggregation Inhibitors/
Aspirin/
aspirin.tw.
exp Stroke/
exp Hemorrhage/
(heart or ventricular) adj3 rate).tw.
*Heart Rate/de [Drug Effects]
rate control.tw.
(Cox or Maze).tw.
(internal adj3 (defibrill$ or cardiover$)).tw.
(radio$ or microwave$).tw.
(cryotherm$ or cryoablat$).tw.
laser$.tw.
(atrial adj3 pac$).tw.
(dual adj3 pac$).tw.
(implant$ adj3 pacemaker$).tw.
(AV nod$ adj3 ablat$).tw.
(implant$ adj3 defibrill$).tw.
(surg$ or catheter$) adj3 ablat$).tw.
surgery/ or thoracic surgery/
defibrillators, implantable/ or implants, experimental/
exp Pulmonary Veins/ pulmonary vein$.tw
exp Catheter Ablation/ or radiofrequency ablation.tw
exp Catheter Ablation or radiofrequency catheter ablation.tw
71
APPENDIX B
Clinical questions
A. Introduction
1. What is the best way to classify atrial fibrillation?
2. What is the epidemiological characteristic of atrial fibrillation?
B. Initial management
1. What are the frequencies of the presenting symptoms?
2. In patients with suspected AF based on an irregular pulse, how accurate
is an ECG in diagnosing AF?
3. Should echocardiography be performed to identify underlying structural
heart disease?
4. In patients with suspected intermittent AF, how effective is ambulatory
ECG compared to an event ECG in diagnosing AF?
5. Which patients with AF would benefit from referral to specialist?
C. Management principles
1. In which patients with persistent AF does rate control result in improved
mortality/morbidity/quality of life over rhythm control?
2. In which patients with persistent AF does rhythm control result in
improved mortality/morbidity/quality of life over rate control?
D. Acute-onset AF
1. In haemodynamically unstable patients presenting with acute AF, what
is the best treatment strategy?
2. In which patients should pill-in-the-pocket therapy be recommended?
3. Does electrical cardioversion versus pharmacological cardioversion
affect rates of thromboembolism, quality of life, success rates?
4. In patients with persistent AF, is amiodarone better than a) flecainide or
b) propafenone for use in cardioversion?
5. In patients with persistent AF is amiodarone better than sotalol for use
in cardioversion?
6. What is the safety and efficacy of the adjunctive administration of
antiarrhythmic drugs for use in electrical cardioversion in comparison to
electrical cardioversion without adjunctive antiarrhythmic drugs?
7. Is a conventional anticoagulation strategy for elective cardioversion as
effective as a transoesophageal echocardiogram plus anticoagulation?
E. Prevention of thromboembolism
1. In patients with AF, what are the risk factors associated with stroke/TIA
and thromboembolism?
2. What is the efficacy of anticoagulation therapy versus placebo for
stroke prevention in: a) paroxysmal AF b) permanent AF c) peri/post
cardioversion to sinus rhythm d) acute/post-op AF e) peri/post stroke f)
72
asymptomatic AF?
3. What is the efficacy of anticoagulation therapy versus antiplatelet
therapy for stroke prevention in: a) paroxysmal AF b) permanent AF c)
peri/post cardioversion to sinus rhythm d) acute/post-op AF e) peri/post
stroke f) asymptomatic AF?
4. What is the efficacy of antiplatelet therapy versus placebo for stroke
prevention in: a) paroxysmal AF b) permanent AF c) peri/post
asymptomatic AF?
5. What is the efficacy of vitamin K antagonist versus novel anticoagulant
for stroke prevention in: a) paroxysmal AF b) permanent AF c) peri/post
asymptomatic AF?
6. What is the role of point-of-care testing and self-monitoring of
anticoagulation.
7. How best to institute anticoagulant and antiplatelet therapy in patients
with AF undergoing percutaneous coronary intervention and non-ST
elevation myocardial infarction
8. In patients with AF what are the risks of long-term oral anticoagulation
therapy?
9. In patients with AF and vitamin K antagonist, what are the risk factors
associated with bleeding?
F. Long-term rate control
1. In patients with permanent AF, what is the efficacy of rate-limiting
calcium antagonists compared with digoxin in rate control?
2. In patients with permanent AF, what is the efficacy of beta-blockers
compared with digoxin in rate control?
3. In patients with permanent AF, what is the efficacy of beta-blockers
compared with rate-limiting calcium antagonists in rate control?
4. In patients with permanent AF, what is the efficacy of rate-limiting
calcium antagonists in combination with digoxin compared with ratelimiting calcium antagonists monotherapy in rate control?
5. In patients with permanent AF, what is the efficacy of beta-blockers in
combination with digoxin compared with beta-blocker monotherapy in
rate control?
6. In patients with permanent AF, what is the efficacy of AV node ablation
with permanent pacemaker therapy in rate control?
G. Long-term rhythm control
1. In patients with paroxysmal AF, is flecainide/propafenone better than
beta-blockers in reducing the frequency of paroxysms?
2. In patients with paroxysmal AF, is amiodarone or sotalol better than
beta-blockers in reducing the frequency of paroxysms?
3. In patients with paroxysmal AF, is flecainide/propefanone better than
amiodarone or sotalol in reducing the frequency of paroxysms?
73
4. In patients with AF, is flecainide or propafenone better than betablockers in maintaining sinus rhythm post cardioversion?
5. In patients with AF, is amiodarone or sotalol better than beta-blockers
in maintaining sinus rhythm post cardioversion?
6. In patients with AF, is flecainide/propafenone better than amiodarone or
sotalol in maintaining sinus rhythm post cardioversion?
7. Which antiarrhythmic agents should be chosen to maintain sinus rhythm
for patients with normal hearts?
8. Which antiarrhythmic agents should be chosen to maintain sinus rhythm
for patients with structural heart disease?
9. What is the efficacy of left atrial catheter ablation and surgical ablation
therapy for rhythm control in patients with a) paroxysmal AF b) persistent
AF?
10. What is the efficacy of cardiac pacing therapy for rhythm control in
patients with paroxysmal AF?
H. Referrals
1. Which patients with AF benefit from referral to specialist services for
assessment and management?
2. Which patients with AF benefit from referral to specialist services for
non-pharmacological treatment or electrophysiological studies?
APPENDIX C
C. WARFARIN IN PRACTICE
Barriers that may prevent people accessing medication and INR testing include:
Financial barriers (including the ability to take time off work)
Travel difficulties
Lack of access to a telephone
Fear or dislike of regular blood tests
Difficulties with general practitioner monitoring.
Possible solutions include the following:
Financial assistance from relevant agencies
Provision of transport (e.g., shuttle service, taxi chits)
Domiciliary testing, either at home or the work place
Testing people in groups at a public health centre using a point-of-care monitor
C.1 INITIATION OF WARFARIN THERAPY
Loading doses are not recommended because they may increase the risk of
bleeding
Initiation of warfarin should be 5 mg daily in most patients (usually achieves INR
2 in 4-5 days)
A starting dose < 5 mg should be considered for patients >65 yrs, liver disease,
malnourished, severe heart failure, 74
or concomitant drugs affecting warfarin
metabolism.
Difficulties with general practitioner monitoring.

Possible solutions include the following:
Financial assistance from relevant agencies
Provision of transport (e.g., shuttle service, taxi chits)
Domiciliary testing, either at home or the work place
Testing people in groups at a public health centre using a point-of-care monitor
C.1 INITIATION OF WARFARIN THERAPY
Loading doses are not recommended because they may increase the risk of
bleeding
Initiation of warfarin should be 5 mg daily in most patients (usually achieves INR
2 in 4-5 days)
A starting dose < 5 mg should be considered for patients >65 yrs, liver disease,
malnourished, severe heart failure, or concomitant drugs affecting warfarin
metabolism.
If overlapping LMWH or heparin with warfarin, overlap for at least 5 days.
Discontinue LMWH or heparin when INR is therapeutic on two consecutive
measurements 24 hr apart.
C.1.2 Frequency of INR Monitoring:
Check baseline INR prior to ordering warfarin
Check INR daily (AM lab) until therapeutic for two consecutive days then twothree times weekly during initiation
C.1.2.1 Standard
Traditionally patients come into the clinic (or the hospital) to have venous blood
drawn for routine laboratory INR determination.
C.1.2.2 Point of Care
Finger tip capillary blood can be used with small, light weight and portable
instruments. The clinical trials result have compared favorably with traditional
INR determination.
Use in anticoagulation clinic.
Home use or Patient Self Test (PST)
x
Need good quality control for point of care INR measurement.

o Patient selection is essential.
o Patients must have long-term indication for anticoagulation therapy.
o Patients must be willing and able to perform self-management.
o Patients must be willing to record results accurately and attend
clinics regularly for quality assurance.
o Patients must demonstrate competence in using the instrument and
interpreting the results.
o Patients must not have shown previous noncompliance in terms of
clinic attendance or medication management.
Can increase INR testing frequency and decrease complications
associated with oral anticoagulation therapy.
C.1.3 Therapeutic INR Ranges:

AF alone: INR 2 3
Prosthetic Heart Valve: INR 2.5 3.5
C.1.4 Average Daily Dose
There are differences among various ethnic
75 groups
Can increase INR testing frequency and decrease complications

associated with oral anticoagulation therapy.
C.1.3 Therapeutic INR Ranges:

AF alone: INR 2 3
Prosthetic Heart Valve: INR 2.5 3.5
C.1.4 Average Daily Dose
There are differences among various ethnic groups
About 4-5 mg/day or 28-35 mg/week for caucasian for target INR of 2.5 (2.0-3.0)
About 3-4 mg/day or 21-28 mg/week for Pacific-Asian (exclude caucasian in this
region). This dose will be less if target INR is recommended at <2.0.
C.1.5 Factors Effecting the Daily Dose
Age ( For caucasian)
o <35 yr ----- 8.1 mg/day.
o 35-49 yr --- 6.4 mg/day.
o 50-59 yr --- 5.1 mg/day.
o 60-69 yr --- 4.2 mg/day.
o >70 yr ----- 3.6 mg/day.
x Genetic. Hereditary warfarin sensitive and resistance.
x Medicine noncompliance.
x Drugs interaction, including herbal medicine.
x Concurrent illness, fever, diarrhea, post op major surgery (i.e.. heart valve
replacement), malignancy, lupus anticoagulants.
x Impaired liver function, CHF with liver congestion.
x Food effect, vitamin K intake, alcohol.
x Hyperthyroidism, renal disease.
x During heparin and direct thrombin inhibitors treatment.
x
C.1.6 Warfarin Initiation

Day 1
(If there is an active or acute thromboembolic condition, warfarin should be
started along with heparin, unless there is a contraindication or patient cannot
take medicine orally. Following warfarin initiation, heparin should be continued
until INR reaches therapeutic level for 2 days).
5 mg (2.5-7.5). This dose is a good choice since it is known that average daily
dose is close to 5 mg. Using higher dose than necessary may lead to bleeding
complication due to rapidly and severely reduce factor VII. It may deplete protein
C too quick, and theoretically can cause hypercoagulable state. The 5 mg size
tablet is recommended for both inpatient and outpatient use, making inpatient to
outpatient transition more convenient. It is the most commonly used size tablet
by the majority of anticoagulation clinics today.
The higher dose warfarin initiation has also been tested successfully by using
normogram. It may be considered in patient who may need shorter period of time
to reach therapeutic INR. It should be done as inpatient. INR have to be done
frequently enough to prevent over anticoagulation and bleeding complication
Use lower dose (2.5 mg).
x >80 yr.
x Concurrent illness.
x On interaction drug.
76
x S/P major surgery, i.e. heart valve surgery.
outpatient transition more convenient. It is the most commonly used size tablet
by the majority of anticoagulation clinics today.
The higher dose warfarin initiation has also been tested successfully by using
normogram. It may be considered in patient who may need shorter period of time
to reach therapeutic INR. It should be done as inpatient. INR have to be done
frequently enough to prevent over anticoagulation and bleeding complication
Use lower dose (2.5 mg).
x >80 yr.
x Concurrent illness.
x On interaction drug.
x S/P major surgery, i.e. heart valve surgery.
x Chronic malnourished.
x Impaired liver function, liver congestion.
Use higher dose (7.5-10.0 mg).
x Young healthy subject.
x In the first two days.
Day 2
A. If INR <1.5, continue the same dose.
B. If INR >1.5, give lower dose (2.5 mg or none)
Day 3
For #A. of Day 2
x If INR <1.5, suggests a higher than average maintenance dose of 5
mg/day or 35 mg/week will be needed. Give higher dose than 5 mg. i.e.7.5
mg for now.
x If INR 1.5-2.0, suggests an average maintenance dose close to 5 mg/day
or close to 35 mg/week will be needed, and continue 5 mg for now.
x If INR >2.0, suggests a lower than average maintenance dose of 5 mg/day
or 35 mg/week will be needed. Give less than 5 mg, i.e.2.5 mg or none for
now.
For #B. of Day 2
x If INR 1.5-2.0, suggests daily dose will be close to or less than 5 mg/day
or close to 35 mg/week or less. May give 5 mg or less for now.
x If INR >2.0, suggests daily dose will be lower than 5 mg/day or less than
35 mg/week. May give 2.5 mg or none for now.
Day 4
If there is no need for heparin therapy, the patient may have been discharged by
now, and warfarin initiation is continued as an outpatient.
x INR 2 times a week until INR is in target range twice in a row, then INR 1
time weekly until INR is in target range twice in a row, then INR 1 time in 2
week until INR is in target range twice in a row, then enter the patient in to
maintenance schedule (usually INR every 4 weeks).
x Patients during an acute illness, or post operative of major surgeries may
be more sensitive to warfarin than when they become more stable.
Out patient (See also "Day 4" above)
x
x
x
Obtain baseline INR

Start with 5 mg daily. See more detail for dose variation in "Inpatient
guideline"
Check INR 2 times a week, or more often if necessary, during the first
week or so. Adjust warfarin dose and timing for INR check as outline in
"Inpatient" guidelines.
77
C.1.7 Ethnic Difference for Chinese-Asian or Pacific-Asian (exclude caucasian in
x
x
x
Obtain baseline INR

Start with 5 mg daily. See more detail for dose variation in "Inpatient
guideline"
Check INR 2 times a week, or more often if necessary, during the first
week or so. Adjust warfarin dose and timing for INR check as outline in
"Inpatient" guidelines.
C.1.7 Ethnic Difference for Chinese-Asian or Pacific-Asian (exclude caucasian in

this region)
Average daily dose of Warfarin for Pacific-Asian (exclude caucasian in this
region) or Chinese-Asian is about 3 mg. Weekly dose is about 21-28 mg,
or lower if "target INR" for various diagnoses are about 0.4-0.5 lower than
those of Caucasian-American-European level.
x "Target INR" for or Pacific-Asian (exclude caucasian in this region) or
Chinese-Asian should be lower than those of Caucasian-AmericanEuropean. The suggest level for nonvalvular atrial fibrillation is 1.6-2.6, to
achieve less combine thromboembolic and major bleeding events. (Need
more database for confirmation)
x Difference in polymorphism of CYP 2C9 and VKORC1which will influence
Warfarin dosage
x
Warfarin Initiation Table for average daily dose of 5 mg and 3 mg further

INR
DAY
DOSE
INPATIENT
OUTPATIENT
Normal
5.0 mg
(2.5 or 7.5-10.0 mg in patients listed in the
text)
5.0 mg
(2.5 or 7.5-10.0 mg in patients listed in the text)
< 1.5
> 1.5
5.0 mg
0.0 - 2.5 mg
5.0 mg
0.0 - 2.5 mg
< 1.5
1.5 - 1.9
2.0 - 3.0
> 3.0
5.0 - 10 mg
2.5 - 5.0 mg
0.0 - 2.5 mg
0.0 mg
(Usually with daily INR)
[If INR is not measured

5.0 mg]
5.0 - 10 mg
2.5 - 5.0 mg
0.0 - 2.5 mg
0.0 mg
INR should be measured today. If INR is not measured,
may use the same dose as day 2, and should not > 5 mg
< 1.5
1.5 - 1.9
2.0 - 3.0
> 3.0
10.0 mg
5.0 - 7.5 mg
0.0 - 5.0 mg
0.0 mg
10.0 mg
5.0 - 7.5 mg
0.0 - 5.0 mg
0.0 mg
INR measurement should be done, if INR on day 3 is < 1.5

or > 3.0
< 1.5
1.5 - 1.9
2.0 - 3.0
> 3.0
10.0 - mg
7.5 - 10.0 mg
0.0 - 5.0 mg
0.0 mg
10.0 - mg
7.5 - 10.0 mg
0.0 - 5.0 mg
0.0 mg
or > 3.0
< 1.5
1.5 - 1.9
2.0 - 3.0
> 3.0
7.5 - 12.5 mg
5.0 - 10.0 mg
0.0 - 7.5 mg
0.0 mg
7.5 - 12.5 mg
5.0 - 10.0 mg
0.0 - 7.5 mg
0.0 mg

or > 3.0
Note: Frequent INR measurement during warfarin initiation helps prevent bleeding from over anticoagulation and helps reaching target INR
sooner.
78
DOSE
DAY
INR
Normal
1
< 1.3
> 1.3
INPATIENT
(Usually with daily INR)
OUTPATIENT
3.0 mg
3.0 mg
3.0 mg
0.0 - 1.5 mg
3.0 mg
0.0 - 1.5 mg
[If INR is not measured
3.0 mg (1.5-4.5)]
< 1.3
1.3 - 1.6
1.6 - 2.6
> 2.6
3.0 - 6 mg
1.5 - 3.0 mg
0.0 - 1.5 mg
0.0 mg
3.0 - 6 mg
1.5 - 3.0 mg
0.0 - 1.5 mg
0.0 mg
INR should be measured today. If INR is not measured,
may use the same dose as day 2, and should not > 3.0 mg
< 1.3
1.3 - 1.6
1.6 - 2.6
> 2.6
4.5 - 6.0 mg
3.0 - 4.5 mg
1.5 - 3.0 mg
0.0 mg
< 1.3
1.3 - 1.6
1.6 - 2.6
> 2.6
6.0 - 7.5 mg
3.0 - 4.5 mg
1.5 - 3.0 mg
0.0 mg
4.5 - 6.0 mg
3.0 - 4.5 mg
0.0 - 3.0 mg
0.0 mg
or > 2.6
6.0 - 7.5 mg
3.0 - 4.5 mg
1.5 - 3.0 mg
0.0 mg
or > 2.6
< 1.3
1.3 - 1.6
1.6 - 2.6
> 2.6
6.0 - 7.5 mg
4.5 - 6.0 mg
1.5 - 3.0 mg
0.0 mg
6.0 - 7.5 mg
4.5 - 6.0 mg
1.5 - 3.0 mg
0.0 mg
or > 2.6
Note: Frequent INR measurement during warfarin initiation helps prevent bleeding from over anticoagulation and helps reaching target INR sooner.
C.1.8
Dose
2.0-3.0)
C.1.8
DoseAdjustments
Adjustmentsfor
forWarfarin
WarfarinMaintenance
Maintenance Therapy
Therapy (Target INR 2.0-3.0)
INR
INR
1.5
1.5
1.5-1.9
1.5-1.9
2.0-3.0
2.0-3.0
3.1-3.9
3.1-3.9
4.0-5.0
4.0-5.0
!5.0
!5.0
Dose Adjustments
Adjustments
Dose
Increaseweekly
weekly dose
dose by
by 20%
Increase
Increaseweekly
weekly dose
dose by 10%
Increase
No change
change
No
Nochange;
change;ififpersistent
persistentdecrease
decrease weekly
weekly dose
dose by
No
by 10-20%
10-20%
Omit11dose;
dose;decrease
decrease weekly
weekly dose
dose by
by 10-20%
Omit
10-20%
Seerecommendations
recommendations for
for managing
managing elevated
elevated INR
See
INR
Whenresume
resumedecrease
decrease weekly
weekly dose
dose 20-50%
20-50%
When
79
C.1.8.1
Recommendationsfor
forManaging
ManagingElevated
ElevatedINRs
INRs or
or Bleeding
Bleeding in Patients
C.1.8.1
Recommendations
C.1.8.1
Recommendations
for Managing Elevated INRs or Bleeding in Patients
Receiving
Warfarin:
Receiving
Warfarin:
Receiving Warfarin:
Condition
Recommendation
Condition
Recommendation
Condition
Recommendation
INR
above
Lowerthe
thedose
doseororomit
omit
doseand
and resume
resume with
with lower
lower dose
INR
above
Lower
aadose
dose
INR
aboverange
Lower
thetherapeutic;
dose
or omitififaonly
dose
and resume
with
lower dose
therapeutic
range when
whenINR
INR
therapeutic;
only
minimally
above
therapeutic
therapeutic
minimally
above
therapeutic
when
INR
therapeutic;
if only
above therapeutic
range,no
nodose
dose
reduction
mayminimally
be required.
required.
but
5;
buttherapeutic
5;
nono range range,
reduction
may
be
but
5; no
significant
bleeding range, no dose reduction may be required.
significant
bleeding
significant
bleeding Omitnext
nextone
oneorortwo
twodoses,
doses,monitor
monitor INR
INR more
more frequently,
frequently,
INR
t but
5 but
INR
t5
9;9;nono Omit
Omit
next one
orlower
two doses,
monitor
INR
more frequently,
INR
t 5 but
9; no and
andresume
resume
with
lower
dosewhen
when
INR
therapeutic.
If
significant
bleeding
with
dose
INR
therapeutic.
If risk
risk of
of
significant
bleeding
and
resume
with
dose and
when
INRvitamin
therapeutic.
If risk
significant bleeding bleeding,
bleeding,
omit
thelower
nextdose
and give
give
vitamin
K 1-2.5
1-2.5
mg
omit
the
next
K
mg of
bleeding,
omit the next dose and give vitamin K 1-2.5 mg
PO.
PO.
PO.
Holdwarfarin
warfarinand
andgive
giveVitamin
VitaminKK 2.5-5
2.5-5 mg
mg orally;
orally; expect
INR
t 9;
Hold
expect
INR
t 9;
nono
warfarin
and
give Vitamin
K 2.5-5Monitor
mg orally;
INR
t 9; nobleeding Hold
substantial
INR
reduction
in 24-48hr.
INRexpect
more
significant
INR reduction in 24-48hr. Monitor INR more
significant bleeding substantial
INRrepeat
reduction
in 24-48hr.
Monitor Resume
INR more
significant bleeding substantial
frequently and
vitamin
K if necessary.
frequently
and
repeat
vitamin
K
if
necessary.
Resume
frequently
repeat vitamin
K if necessary.
Resume
warfarin atand
an adjusted
dose when
INR therapeutic.
warfarin
warfarinatatan
anadjusted
adjusteddose
dosewhen
when INR
INR therapeutic.
therapeutic.
Serious bleeding at Hold warfarin and give vitamin K 10 mg slow IV infusion,
Serious
bleeding
warfarin
give
vitamin
KK 10
slow
infusion,
Serious
bleeding
Hold
warfarinand
and
give
vitamin
10 mg
mg
slow IV
IVconcentrate
infusion,
any elevation
ofatat Hold
supplemented
with
FFP,
prothrombin
complex
any
elevation
supplemented
with
prothrombin
complex
concentrate
any
elevationofof
supplemented
withFFP,
FFP,
prothrombin
complex
concentrate
INR
or rVIIa, depending
on urgency
of situation.
Vitamin
K can
INR
oror
rVIIa,
depending
on
urgency
of
situation.
Vitamin
K can
can
INR
rVIIa,
depending
on
urgency
of
situation.
Vitamin
K
be repeated q12hr
be
repeated
q12hr
be
repeated
q12hr
Life threatening
Hold warfarin and give FFP, prothrombin complex
Life
threatening
Hold
warfarin
give
FFP,
complex
Life
threatening
Hold
warfarinand
and
give
FFP,prothrombin
prothrombin
complex
bleeding
concentrate,
or
rVIIa
supplemented
with vitamin
K 10 mg
bleeding
concentrate,
ororrVIIa
supplemented
with
vitamin
10
mg
bleeding
concentrate,
rVIIa
supplemented
withdepending
vitamin K
K 10
slow IV infusion.
Repeat,
if necessary,
on mg
INR.
slow
on INR.
INR.
slowIVIVinfusion.
infusion. Repeat,
Repeat,ififnecessary,
necessary, depending
depending on
C.1.9 Interruption of Warfarin Therapy for Surgery

C.1.9
Interruption
C.1.9
InterruptionofofWarfarin
WarfarinTherapy
Therapyfor
forSurgery
Surgery
Condition
Condition
LowCondition
risk
of
Low
risk
ofof
Low
risk
thromboembolism
thromboembolism
thromboembolism
Moderate risk of
Moderate
riskofof
Moderate
risk
thromboembolism
thromboembolism
thromboembolism
High risk of
High
risk
thromboembolism
High
risk
ofof
thromboembolism
thromboembolism
Low risk of
Low
risk
bleeding
Low
risk
ofof
bleeding
bleeding
Urgent surgical or
Urgent
surgicaloror
other surgical
invasive
Urgent
other
invasive
procedure
(within
other
invasive
procedure
(within
12
hours)(within
procedure
12 hours)
12Urgent
hours)surgical or
Urgent surgical or
Urgent surgical or
Recommendations
Recommendations
Stop warfarin 5 daysRecommendations
before surgery allowing INR to return
Stop
warfarin
55days
before
surgery
return
Stop
warfarin
days
before
surgery
allowing
to return
to near
normal.
Bridge
therapy
with allowing
low
doseINR
LMWH
or no
toto
near
no
nearnormal.
normal. Bridge
Bridgetherapy
therapy with
with low
low dose
dose LMWH or no
bridging.
bridging.
bridging.
Stop warfarin 5 days before surgery allowing INR to fall,
Stop
warfarin
dayswith
before
surgery allowing
allowing
to fall,
Stop
55days
before
surgery
INR 2-3
startwarfarin
bridge
therapy
therapeutic
dose LMWH
days
start
bridge
therapy
withtherapeutic
therapeutic
dose LMWH 2-3
priorbridge
to surgery
(or when
INR is sub-therapeutic).
start
therapy
with
dose
days
2-3 days
prior
surgery
(orwhen
when
INRisis24
sub-therapeutic).
Administer
last(or
dose
of LMWH
hrs before surgery.
prior
totosurgery
INR
sub-therapeutic).
Administer
last
dose
of
LMWH
24
hrs
before
surgery.
Stop warfarin
daysofbefore
surgery
INR to fall,
Administer
last 5dose
LMWH
24 hrsallowing
before surgery.
Stop
warfarin
dayswith
before
surgery allowing
allowing
INR 2-3
to
startwarfarin
bridge
therapy
therapeutic
dose LMWH
days
Stop
55days
before
surgery
INR
to fall,
fall,
start
bridge
therapy
with
therapeutic
dose
LMWH
priorbridge
to surgery
(or when
INR is sub-therapeutic).
start
therapy
with therapeutic
dose LMWH 2-3
2-3 days
days
prior
to
surgery
(or
when
INR
is
sub-therapeutic).
Administer
last(or
dose
of LMWH
before surgery.
prior
to surgery
when
INR is 24hrs
sub-therapeutic).
Administer
last
dose
of
LMWH
24hrs
before
surgery.
Lower warfarin
operate
at an
INR of
1.3-1.5; the
Administer
last dose ofand
LMWH
24hrs
before
surgery.
Lower
warfarin
doseand
and
operate
at an
ansurgery;
INR of
of 1.3-1.5;
1.3-1.5;
dose warfarin
may
be lowered
4-5operate
days before
warfarinthe
can
Lower
dose
at
INR
the
dose
may
be
lowered
4-5
days
before
surgery;
warfarin
can
be
restarted
post-op,
supplement
with
LMWH
if
necessary.
dose may be lowered 4-5 days before surgery; warfarin
can
restartedpost-op,
post-op,supplement
supplement with
with LMWH
LMWH ifif necessary.
necessary.
beberestarted
For immediate reversal give FFP, prothrombin complex
For
immediate
reversal
give
FFP, prothrombin
prothrombin
complex
concentrate
inreversal
additiongive
to vitamin
K 2.5-5 mg po
or by slow
For
immediate
FFP,
complex
concentrate
addition to vitamin K 2.5-5 mg po or by slow
IV infusion. ininaddition
concentrate
to vitamin K 2.5-5 mg po or by slow
IV infusion.
IV infusion.
If surgery is urgent but can be delayed for 18-24 hrs give
80
other invasive
procedure (within
18-24 hours)
vitamin K 2.5- 5 mg po or by slow IV infusion. If INR is still

high, additional vitamin K 1-2 mg po can be given.
Low risk: VTE: Single VTE occurred >12 months ago and no other risk factors,
AF: (CHADS2 score 0-2) without a history of stroke or other risk factors, Mech
heart valve: bileaflet aortic valve without AF and no other risk factors for stroke.
Moderate risk: VTE: VTE within 3-12 months, non-severe thrombophilic
conditions, recurrent VTE, active cancer, AF: (CHADS2 score 3 or 4), Mech heart
valve: bileaflet aortic valve and one of the following: AF, prior stroke or TIA, HTN,
DM, CHF, age >75 yr.
High risk: VTE: recent (within 3mo) VTE, severe thrombophilia, AF:(CHADS2
score 5 or 6), recent (within 3 months) stroke or TIA, rheumatic valvular heart
disease,
Mech heart valve: any mitral valve prosthesis, older aortic valve prosthesis
(caged-ball or tilting disc), recent (within 6 months) stroke or TIA
x
x
Resume warfarin therapy 12-24 hrs after surgery and when there is
adequate hemostasis.
Resume bridge therapy:
o Minor surgery or other invasive procedure and receiving therapeutic
dose LMWH: Resume 24 hrs after the procedure when there is
adequate hemostasis
o Major surgery or high bleeding risk surgery/procedure where postop therapeutic dose LMWH is planned: delay initiation of
therapeutic dose LMWH for 48-72 hours after surgery when
hemostasis is secured or administering low dose LMWH after
surgery when hemostasis is secured or completely avoiding LMWH
after surgery.
81
APPENDIX D
Vaughn Williams Classification of Antiarrhythmic Drugs
Type IA
Disopyramide
Procainamide
Quinidine
Type IB
Lignocaine
Mexilitine
Type IC
Flecainide
Propafenone
Type II
Beta blockers (e.g. propranolol)
Type III
Amiodarone
Dronedarone
Bretylium
Dofetilide
Ibutilide
Sotalol
Type IV
Nondihydropyridine calcium channel antagonist (verapamil and diltiazem)
Table includes compounds introduced after publication of the original classification.
82
Glossary
ACEI
Angiotensin Converting Enzyme Inhibitor
ACS
Acute Coronary Syndrome
AF
Atrial fibrillation
AFl
Atrial Flutter
AFFIRM
Atrial Fibrillation Follow-up Investigation of Rhythm

Management
AP
Accessory Pathway
AV
Atrioventricular
ARB
Angiotensin Receptor Blocker
BAFTA
Birmingham Atrial Fibrillation Treatment of the Aged
bpm
Beats per minute
CCB
Calcium Channel Blocker
CAD Coronary Artery Disease

CCS-SAF
Canadian Cardiovascular Society Severity in Atrial Fibrillation
CHA2DS2VASc
Congestive Heart Failure, Hypertension, Age, Diabetes

Mellitus and Stroke, Vascular Disease
CHADS2
Congestive Heart Failure, Hypertension, Age, Diabetes

Mellitus and Stroke
CHF
Congestive Heart Failure
COPD
Chronic Obstructive Pulmonary Disease
CPR
Cardiopulmonary Resuscitation
CRT
Cardiac Resynchronisation Therapy
CT
Computed tomography
CV
Cardioversion
CYP
Cytochrome P
DCCV
Direct Current Cardioversion
DM
Diabetes Mellitus
EAPCI
European Association of Percutaneous Cardiovascular

Interventions
ECG
Electrocardiogram
EHRA
European Heart Rhythm Association
GPI
Glycoprotein IIb/IIIa Inhibitor
HAS-BLED
Hypertension, Abnormal renal and liver function, Stroke,

Bleeding, Labile INR, Elderly, Drugs
HCM
Hypertrophic Cardiomyopathy
HF
Heart Failure
HOT CAF
HOw to Treat Chronic Atrial Fibrillation
HTN
Hypertension
ICD
Implantable Cardioverter Defibrillator

83
INR
International Normalised Ratio
IV
Intravenous
J-RHYTHM
Japanese Rhythm Management Trial for Atrial Fibrillation
LA
Left atrium
LAA
Left atrial appendage
LMWH
Low molecular weight heparin
LoE
Level of Evidence
LV
Left ventricle
LVEF
Left Ventricular Ejection Fraction
LVH
Left Ventricular Hypertrophy
MI
Myocardial Infarction
N/A
Not available
ND
Not Determined
NYHA
New York Heart Association
OAC
Oral Anticoagulant
PAD
Peripheral Artery Disease
PAF
Paroxysmal atrial fibrillation
PCI
Percutaneous Intervention
PIAF
Pharmacological Intervention in Atrial Fibrillation
PUFA
Polyunsaturated fatty acids
PVI
Pulmonary Vein Isolation
RACE
RAte Control versus Electrical CardioversionFor Persistent

Atrial Fibrillation
RE-LY
Randomised Evaluation of Long-Term Anticoagulation

Therapy
SCD
Sudden Cardiac Death
SR
Sinus Rhythm
STAF
Strategies of Treatment of Atrial Fibrillation
TE
Thromboembolism
TE risk
Thrombo-embolic risk
TIA
Transient ischemic attack
TOE
Transesophageal echocardiogram
TTE
Transthoracic echocardiogram
UFH
Unfractionated Heparin
VHD
Valvular Heart Disease
VKA
Vitamin K Antagonist
VTE
Venous Thromboembolism Prophylaxis
WPW
Wolff-Parkinson-White Syndrome
84
References from ESC 2010 AF Guidelines

(1) Jahangir A, Lee V, Friedman PA, Trusty JM, Hodge DO, Kopecky SL, Packer DL,
Hammill SC, Shen WK, Gersh BJ. Long-term progression and outcomes with aging in
patients with lone atrial fibrillation: a 30-year follow-up study. Circulation
2007;115:30503056.
(2) Kirchhof P, Auricchio A, Bax J, Crijns H, Camm J, Diener HC, Goette A, Hindricks G,
Hohnloser S, Kappenberger L, Kuck KH, Lip GY, Olsson B, Meinertz T, Priori S, Ravens
U, Steinbeck G, Svernhage E, Tijssen J, Vincent A, Breithardt G. Outcome parameters
for trials in atrial fibrillation: executive
summary. Recommendations from a consensus conference organized by the German
Atrial Fibrillation Competence NETwork (AFNET) and the European Heart Rhythm
Association (EHRA). Eur Heart J 2007;28:28032817.
(3) Stewart S, Hart CL, Hole DJ, McMurray JJ. Population prevalence, incidence, and
predictors of atrial fibrillation in the Renfrew/Paisley study. Heart 2001;86:516521.
(4) Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE.
Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm
management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial
Fibrillation (ATRIA) Study. JAMA 2001;285:23702375.
(5) Stewart S, Hart CL, Hole DJ, McMurray JJ. A population-based study of the
longterm risks associated with atrial fibrillation: 20-year follow-up of the Renfrew/Paisley
study. Am J Med 2002;113:359364.
(6) Hylek EM, Go AS, Chang Y, Jensvold NG, Henault LE, Selby JV, Singer DE. Effect
of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N
Engl J Med 2003;349:10191026.
(7) Knecht S, Oelschlager C, Duning T, Lohmann H, Albers J, Stehling C, HeindelW,
Breithardt G, Berger K, Ringelstein EB, Kirchhof P, Wersching H. Atrial fibrillation in
stroke-free patients is associated with memory impairment and hippocampal atrophy.
Eur Heart J 2008;29 21252132.
(8) Friberg L, Hammar N, Rosenqvist M. Stroke in paroxysmal atrial fibrillation:report
from the Stockholm Cohort of Atrial Fibrillation. Eur Heart J 2010;31:967975.
(9) Thrall G, Lane D, Carroll D, Lip GY. Quality of life in patients with atrial fibrillation:a
systematic review. Am J Med 2006;119:448 e1e19.
(10) Hobbs FD, Fitzmaurice DA, Mant J, Murray E, Jowett S, Bryan S, Raftery J, Davies
M, Lip G. A randomised controlled trial and cost-effectiveness study of systematic
screening (targeted and total population screening) versus routine practice for the
detection of atrial fibrillation in people aged 65 and over. The SAFE study. Health
Technol Assess 2005;9:iiiiv, ixx, 174.
(11) Jabaudon D, Sztajzel J, Sievert K, Landis T, Sztajzel R. Usefulness of ambulatory
7-day ECG monitoring for the detection of atrial fibrillation and flutter after acute stroke
and transient ischemic attack. Stroke 2004;35:16471651.
(12) Binici Z, Intzilakis T, Nielsen OW, Kober L, Sajadieh A. Excessive Supraventricular
ectopic activity and increased risk of atrial fibrillation and stroke. Circulation
2010;121:19041911.
(13) Klein AL, Grimm RA, Murray RD, Apperson-Hansen C, Asinger RW, Black IW,
Davidoff R, Erbel R, Halperin JL, Orsinelli DA, Porter TR, Stoddard MF. Use of
transesophageal echocardiography to guide cardioversion in patients with atrial
fibrillation. N Engl J Med 2001;344:14111420.
85
(14) Fitzmaurice DA, Hobbs FD, Jowett S, Mant J, Murray ET, Holder R, Raftery
JP,Bryan S, Davies M, Lip GY, Allan TF. Screening versus routine practice in detection
of atrial fibrillation in patients aged 65 or over: cluster randomised controlledtrial. BMJ
2007;335:383.
(15) Dorian P, Guerra PG, Kerr CR, ODonnell SS, Crystal E, Gillis AM, Mitchell LB, Roy
D, Skanes AC, Rose MS, Wyse DG. Validation of a new simple scale to measure
symptoms in atrial fibrillation: the Canadian Cardiovascular Society Severity in Atrial
Fibrillation scale. Circ Arrhythm Electrophysiol 2009;2:218224.
(16) Kirchhof P, Bax J, Blomstrom-Lundquist C, Calkins H, Camm AJ, Cappato R, Cosio
F, Crijns H, Diener HC, Goette A, Israel CW, Kuck KH, Lip GY, Nattel S, Page RL,
Ravens U, Schotten U, Steinbeck G, Vardas P, Waldo A, Wegscheider K, Willems S,
Breithardt G. Early and comprehensive management
nd
of atrial fibrillation: executive summary of the proceedings from the 2 AFNET-EHRA
consensus conference Research perspectives in AF. Eur Heart J 2009;30:p2969
2977c.
(17) Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, PooleWilson PA, Stromberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A,
Nieminen M, Priori SG, Swedberg K, Vahanian A, Camm J, De Caterina R, Dean V,
Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S,
Tendera M, Widimsky P, Zamorano JL. ESC Guidelines for the diagnosis and treatment
of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment
of
Acute and Chronic Heart Failure 2008 of the European Society of Cardiology.
Developed in collaboration with the Heart Failure Association of the ESC (HFA) and
endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J
2008;29:23882442.
(18) Calkins H, Brugada J, Packer DL, Cappato R, Chen SA, Crijns HJ, Damiano RJ Jr,
Davies DW, Haines DE, Haissaguerre M, Iesaka Y, Jackman W, Jais P, Kottkamp H,
Kuck KH, Lindsay BD, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee
K, Natale A, Pappone C, Prystowsky E, Raviele A, Ruskin JN, Shemin RJ, Calkins H,
Brugada J, Chen SA, Prystowsky EN, Kuck KH, Natale A, Haines DE, Marchlinski FE,
Calkins H, Davies DW, Lindsay BD, McCarthy PM, Packer DL, Cappato R, Crijns HJ,
Damiano RJ Jr, Haissaguerre M, Jackman WM, Jais P, Iesaka Y, Kottkamp H, Mont L,
Morady F, Nademanee K, Pappone C, Raviele A, Ruskin JN, Shemin RJ.
HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of
Atrial Fibrillation: Recommendations for Personnel, Policy, Procedures and Follow-Up: a
report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation
of Atrial Fibrillation developed in partnership with the European Heart Rhythm
Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); in
collaboration with the American College of Cardiology (ACC), American Heart
Association (AHA), and the Society of Thoracic
Surgeons (STS). Endorsed and approved by the governing bodies of the American
College of Cardiology, the American Heart Association, the European Cardiac
Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic
Surgeons, and the Heart Rhythm Society. Europace 2007;9:335379.
(19) Jabaudon D, Sztajzel J, Sievert K, Landis T, Sztajzel R. Usefulness of ambulatory
7-day ECG monitoring for the detection of atrial fibrillation and flutter after acute stroke
and transient ischemic attack. Stroke 2004;35:16471651.
(20) Haverkamp W, Breithardt G, Camm AJ, Janse MJ, Rosen MR, Antzelevitch C,
Escande D, Franz M, Malik M, Moss A, Shah R. The potential for QT prolongation and
proarrhythmia by non-antiarrhythmic drugs: clinical and regulatory implications. Report
on a policy conference of the European Society of Cardiology. Eur Heart J
2000;21:12161231.
86
(21) Singh BN, Singh SN, Reda DJ, Tang XC, Lopez B, Harris CL, Fletcher RD, Sharma
SC, Atwood JE, Jacobson AK, Lewis HD Jr, Raisch DW, Ezekowitz MD. Amiodarone
versus sotalol for atrial fibrillation. N Engl J Med 2005;352:18611872.
(22) Hohnloser SH, Kuck KH, Lilienthal J. Rhythm or rate control in atrial fibrillationPharmacological Intervention in Atrial Fibrillation (PIAF): a randomized trial. Lancet
2000;356:17891794.
(23) AFFIRM Investigators. A comparison of rate control and rhythm control in patients
with atrial fibrillation. N Engl J Med 2002;347:18251833.
(24) Van Gelder IC, Hagens VE, Bosker HA, Kingma H, Kamp O, Kingma T, Said SA,
Darmanata JI, Timmermanns AJM, Tijssen JGP, Crijns HJ. A comparison of rate control
and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med
2002;347:18341840.
(25) Carlsson J, Miketic S, Windeler J, Cuneo A, Haun S, Micus S, Walter S, Tebbe U,
and the STAF Investigators. Randomized trial of rate-control versus rhythmcontrol in
persistent atrial fibrillation. J Am Coll Cardiol 2003;41:16901696.
(26) Opolski G, Torbicki A, Kosior DA, Szulc M,Wozakowska-Kaplon B, Kolodziej P,
Achremczyk P. Rate control vs rhythm control in patients with nonvalvular persistent
atrial fibrillation: the results of the Polish How to Treat Chronic Atrial Fibrillation (HOT
CAFE) Study. Chest 2004;126:476486.
(27) Roy D, Talajic M, Nattel S, Wyse DG, Dorian P, Lee KL, Bourassa MG, Arnold JM,
Buxton AE, Camm AJ, Connolly SJ, Dubuc M, Ducharme A, Guerra PG, Hohnloser SH,
Lambert J, Le Heuzey JY, OHara G,
Pedersen OD, Rouleau JL, Singh BN, Stevenson LW, Stevenson WG, Thibault B,
Waldo AL. Rhythm control versus rate control for atrial fibrillation and heart failure. N
Engl J Med 2008;358:26672677.
(28) Ogawa S, Yamashita T, Yamazaki T, Aizawa Y, Atarashi H, Inoue H, Ohe T, Ohtsu
H, Okumura K, Katoh T, Kamakura S, Kumagai K, Kurachi Y, Kodama I, Koretsune Y,
Saikawa T, Sakurai M, Sugi K, Tabuchi T, Nakaya H, Nakayama T, Hirai M, Fukatani M,
Mitamura H. Optimal treatment strategy
for patients with paroxysmal atrial fibrillation: J-RHYTHM Study. Circ J 2009; 73:242
248.
(29) Hsu LF, Jais P, Sanders P, Garrigue S, Hocini M, Sacher F, Takahashi Y, Rotter M,
Pasquie JL, Scavee C, Bordachar P, Clementy J, Haissaguerre M. Catheter ablation for
atrial fibrillation in congestive heart failure. N Engl J Med 2004;351:23732383.
(30) Khan MN, Jais P, Cummings J, Di Biase L, Sanders P, Martin DO, Kautzner J, Hao
S, Themistoclakis S, Fanelli R, Potenza D, Massaro R, Wazni O, Schweikert R, Saliba
W, Wang P, Al-Ahmad A, Beheiry S, Santarelli P, Starling RC, Dello Russo A,
Pelargonio G, Brachmann J, Schibgilla V, Bonso A, Casella M, Raviele A, Haissaguerre
M, Natale A. Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. N
Engl J Med 2008;359:17781785.
(31) Wilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, Macle L,
Daoud EG, Calkins H, Hall B, Reddy V, Augello G, Reynolds MR, Vinekar C, Liu CY,
Berry SM, Berry DA. Comparison of antiarrhythmic drug therapy and radiofrequency
catheter ablation in patients with paroxysmal atrial fibrillation:a randomized controlled
trial. JAMA 2010;303:333340.
(32) Talajic M, Khairy P, Levesque S, Connolly SJ, Dorian P, Dubuc M, Guerra PG,
Hohnloser SH, Lee KL, Macle L, Nattel S, Pedersen OD, Stevenson LW, Thibault B,
Waldo AL, Wyse DG, Roy D. Maintenance of sinus rhythm and survival in patients with
heart failure and atrial fibrillation. J Am Coll Cardiol 2010;55:17961802.
87
(33) UK Resuscitation Council. Advanced Life Support (ALS) Provider Manual (4th
edition) London:
Resuscitation Council (UK) Trading Ltd;2004.
(34) Segal JB, McNamara RL, Miller MR, Kim N, Goodman SN, Powe NR, Robinson K,
Yu D, Bass EB. The evidence regarding the drugs used for ventricular rate control. J
Fam Pract 2000;49:4759.
(35) Hou ZY, Chang MS, Chen CY, Tu MS, Lin SL, Chiang HT, Woosley RL. Acute
treatment of recent-onset atrial fibrillation and flutter with a tailored dosing regimen of
intravenous amiodarone. A randomized, digoxin-controlled study. Eur Heart J
1995;16:521528.
(36) Reisinger J, Gatterer E, LangW, Vanicek T, Eisserer G, Bachleitner T, Niemeth C,
Aicher F, Grander W, Heinze G, Kuhn P, Siostrzonek P. Flecainide versus ibutilide for
immediate cardioversion of atrial fibrillation of recent onset. Eur Heart J 2004;25:1318
1324.
(37) Khan IA. Single oral loading dose of propafenone for pharmacological
cardioversion of recent-onset atrial fibrillation. J Am Coll Cardiol 2001;37:542547.
(38) Martinez-Marcos FJ, Garcia-Garmendia JL, Ortega-Carpio A, Fernandez-Gomez
JM, Santos JM, Camacho C. Comparison of intravenous flecainide, propafenone, and
amiodarone for conversion of acute atrial fibrillation to sinus rhythm. Am J Cardiol
2000;86:950953.
(39) Chevalier P, Durand-Dubief A, Burri H, Cucherat M, Kirkorian G, Touboul P.
Amiodarone versus placebo and class Ic drugs for cardioversion of recent-onset atrial
fibrillation: a meta-analysis. J Am Coll Cardiol 2003;41:255262.
(40) Vardas PE, Kochiadakis GE, Igoumenidis NE, Tsatsakis AM, Simantirakis EN,
Chlouverakis GI. Amiodarone as a first-choice drug for restoring sinus rhythm in
patients with atrial fibrillation: a randomized, controlled study. Chest 2000;117:1538
1545.
(41) Bianconi L, Castro A, Dinelli M, Alboni P, Pappalardo A, Richiardi E, Santini M.
Comparison of intravenously administered dofetilide versus amiodarone in the acute
termination of atrial fibrillation and flutter. A multicentre, randomized, double-blind,
placebo-controlled study. Eur Heart J 2000;21:12651273.
(42) Alboni P, Botto GL, Baldi N, Luzi M, Russo V, Gianfranchi L, Marchi P, Calzolari M,
Solano A, Baroffio R, Gaggioli G. Outpatient treatment of recent-onset atrial fibrillation
with the pill-in-the-pocket approach. N Engl J Med 2004;351:23842391.
(43) Kirchhof P, Eckardt L, Loh P, Weber K, Fischer RJ, Seidl KH, Bocker D, Breithardt
G, Haverkamp W, Borggrefe M. Anteriorposterior versus anteriorlateral electrode
positions for external cardioversion of atrial fibrillation:a randomised trial. Lancet
2002;360:12751279.
(44) Oral H, Souza JJ, Michaud GF, Knight BP, Goyal R, Strickberger SA, Morady
F.Facilitating transthoracic cardioversion of atrial fibrillation with ibutilide pretreatment. N
Engl J Med 1999;340:18491854.
(45) Manios EG, Mavrakis HE, Kanoupakis EM, Kallergis EM, Dermitzaki DN,
Kambouraki DC, Vardas PE. Effects of amiodarone and diltiazem on persistent atrial
fibrillation conversion and recurrence rates: a randomized controlled study. Cardiovasc
Drugs Ther 2003;17:3139.
(46) Bianconi L, Mennuni M, Lukic V, Castro A, Chieffi M, Santini M. Effects of oral
propafenone administration before electrical cardioversion of chronic atrial fibrillation: a
placebo-controlled study. J Am Coll Cardiol 1996;28:700706.
88
(47) Gulamhusein S, Ko P, Carruthers SG, Klein GJ. Acceleration of the ventricular

response during atrial fibrillation in the WolffParkinsonWhite syndrome after
verapamil. Circulation 1982;65:348354.
(48) Fetsch T, Bauer P, Engberding R, Koch HP, Lukl J, Meinertz T, Oeff M, Seipel L,
Trappe HJ, Treese N, Breithardt G. Prevention of atrial fibrillation after cardioversion:
results of the PAFAC trial. Eur Heart J 2004;25:13851394.
(49) Hughes M, Lip GY. Stroke and thromboembolism in atrial fibrillation: a systematic
review of stroke risk factors, risk stratification schema and cost effectiveness data.
Thromb Haemost 2008;99:295304.
(50) Stroke in AF working group. Independent predictors of stroke in patients with atrial
fibrillation: a systematic review. Neurology 2007;69:546554.
(51) Gage BF, Waterman AD, Shannon W, Boechler M, Rich MW, Radford MJ.
Validation of clinical classification schemes for predicting stroke: results from the
National Registry of Atrial Fibrillation. JAMA 2001;285:28642870.
(52) Go AS, Hylek EM, Chang Y, Phillips KA, Henault LE, Capra AM, Jensvold NG,
Selby JV, Singer DE. Anticoagulation therapy for stroke prevention in atrial
fibrillation:how well do randomized trials translate into clinical practice? JAMA
2003;290:26852692.
(53) Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk
stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel
risk factor-based approach: the Euro Heart Survey on atrial fibrillation. Chest
2010;137:263272.
(54) Lip GY, Frison L, Halperin J, Lane D. Identifying patients at risk of stroke despite
anticoagulation. Stroke 2010;in press.
(55) Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent
stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007;146:857
867.
(56) Connolly S, Pogue J, Hart R, Pfeffer M, Hohnloser S, Chrolavicius S, Yusuf S.
Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial
fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE
W): a randomised controlled trial. Lancet 2006;367:19031912.
(57) Connolly SJ, Pogue J, Hart RG, Hohnloser SH, Pfeffer M, Chrolavicius S, Yusuf S.
Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N Engl J Med
2009;360:20662078.
(58) Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J,
Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis
BS, Darius H, Diener HC, Joyner CD,Wallentin L. Dabigatran versus warfarin in patients
with atrial fibrillation. N Engl J Med 2009;361:11391151.
(59) Hart RG, Benavente O, McBride R, et al. Antithrombotic therapy to prevent stroke
in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999;131:492501.
(60) The effect of low-dose warfarin on the risk of stroke in patients with non rheumatic
atrial fibrillation. The Boston Area Anticoagulation Trialfor Atrial Fibrillation Investigators.
N Engl J Med 1990;323:150511.
(61) Petersen P, Boysen G, Godtfredsen J, et al. Placebo-controlled, randomized trial of
warfarin and aspirin for prevention of thromboembolic complications in chronic atrial
fibrillation. The Copenhagen AFASAK study. Lancet 1989;1:1759.
89
(62) Connolly SJ, Laupacis A, Gent M, et al. Canadian Atrial Fibrillation Anticoagulation
(62) Connolly
Laupacis
A, Gent
M, et al. Canadian
Atrial Fibrillation Anticoagulation
(CAFA)
Study.SJ,
J Am
Coll Cardiol
1991;18:349
55.
(CAFA) Study. J Am Coll Cardiol 1991;18:349 55.
(63) Ezekowitz MD, Bridgers SL, James KE, et al. Warfarin in the prevention of stroke
(63)
Ezekowitz
Bridgers SL,
James
KE, et al. Warfarin
in theStroke
prevention
of stroke
associated
withMD,
nonrheumatic
atrial
fibrillation.Veterans
Affairs
Prevention
in
associated with
nonrheumatic
Nonrheumatic
Atrial
Fibrillation atrial fibrillation.Veterans Affairs Stroke Prevention in
Nonrheumatic[published
Atrial Fibrillation
Investigators
erratum appears in N Engl J Med 1993; 328(2):148]. N Engl J
Investigators
[published
Med
1992;327:1406
12.erratum appears in N Engl J Med 1993; 328(2):148]. N Engl J
Med 1992;327:1406 12.
(64) Singer DE, Albers GW, Dalen JE, Fang MC, Go AS, Halperin JL, Lip GY, Manning
(64) Singer
DE, Albers
GW, in
Dalen
Fang MC,American
Go AS, Halperin
Lip GY,
Manning
WJ.
Antithrombotic
therapy
atrialJE,
fibrillation:
College JL,
of Chest
Physicians
WJ. Antithrombotic
therapy
in atrial
fibrillation:
College
of Chest Physicians
Evidence-Based
Clinical
Practice
Guidelines
(8thAmerican
Edition). Chest
2008;133:546S592S
Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:546S592S
(65) Lip GY, Golding DJ, Nazir M, Beevers DG, Child DL, Fletcher RI. A survey of atrial
(65) Lip GY,
Golding practice:
DJ, Nazirthe
M, West
Beevers
DG, ChildAtrial
DL, Fletcher
RI.Project.
A surveyBrofJ atrial
fibrillation
in general
Birmingham
Fibrillation
Gen
fibrillation
in general practice: the West Birmingham Atrial Fibrillation Project. Br J Gen
Pract
1997;47:285289.
Pract 1997;47:285289.
(66) Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, Flachskampf
(66)
Vahanian
H, Bax
Butchart
Dion R,L,Filippatos
G,Guidelines
Flachskampf
F,
Hall
R, Iung A,
B, Baumgartner
Kasprzak J, Nataf
P,J,Tornos
P, E,
Torracca
Wenink A.
on
F, Hall
R, Iung B, Kasprzak
Nataf disease:
P, Tornosthe
P, Torracca
L, Wenink
Guidelines on
the
management
of valvularJ, heart
Task Force
on the A.
Management
of
the management
of valvular
disease: the
Task Force
on the Management
Valvular
Heart Disease
of heart
the European
Society
of Cardiology.
Eur Heart of
J
Valvular Heart Disease of the European Society of Cardiology. Eur Heart J
2007;28:230268.
2007;28:230268.
(67) Miyasaka Y, Barnes ME, Gersh BJ, Cha SS, Bailey KR, Abhayaratna WP, Seward
(67) Tsang
Miyasaka
Barnes ME,
Gersh
BJ, Cha SS,
Baileyfibrillation
KR, Abhayaratna
WP, County,
Seward
JB,
TS.Y,Secular
trends
in incidence
of atrial
in Olmsted
JB, Tsang TS.
in incidenceonof the
atrial
fibrillationforin future
Olmsted
County,
Minnesota,
1980Secular
to 2000,trends
and implications
projections
prevalence.
Minnesota, 2006;114:119125.
1980 to 2000, and implications on the projections for future prevalence.
Circulation
Circulation 2006;114:119125.
(68) Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY, Murray E. Warfarin
(68) Mant
J, Hobbs
FD, Fletcher
K, Roalfe
A, Fitzmaurice
D, Lip GY,
Murray E.with
Warfarin
versus
aspirin
for stroke
prevention
in an
elderly community
population
atrial
versus
aspirin
for stroke prevention
in an Treatment
elderly community
population
with atrial
fibrillation
(the Birmingham
Atrial Fibrillation
of the Aged
Study, BAFTA):
a
fibrillation (the
Birmingham
Atrial Fibrillation
Treatment of the Aged Study, BAFTA): a
randomised
controlled
trial. Lancet
2007;370:493503.
randomised controlled trial. Lancet 2007;370:493503.
(69) Sato H, Ishikawa K, Kitabatake A, Ogawa S, Maruyama Y, Yokota Y, Fukuyama T,
(69)Y,
Sato
H, Ishikawa
K, Kitabatake
A, Ogawa
S, Maruyama
Y, K,
Yokota
Y, Fukuyama
T,
Doi
Mochizuki
S, Izumi
T, Takekoshi
N, Yoshida
K, Hiramori
Origasa
H, Uchiyama
DoiMatsumoto
Y, Mochizuki
Izumi T, Takekoshi
N, Low-dose
Yoshida K,aspirin
Hiramori
Origasa H,ofUchiyama
S,
M,S,Yamaguchi
T, Hori M.
forK,prevention
stroke in
S, Matsumoto
M, with
Yamaguchi
T, Hori M.Japan
Low-dose
for prevention
of stroke
in
low-risk
patients
atrial fibrillation:
Atrialaspirin
Fibrillation
Stroke Trial.
Stroke
low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial. Stroke
2006;37:447451.
2006;37:447451.
(70) Maisel WH. Autonomic modulation preceding the onset of atrial fibrillation. J Am
(70) Cardiol
Maisel 2003;42:1269
WH. Autonomic
modulation preceding the onset of atrial fibrillation. J Am
Coll
70.
Coll Cardiol 2003;42:1269 70.
(71) Israel CW, Gronefeld G, Ehrlich JR, et al. Long-term risk of recurrent atrial
(71)
IsraelasCW,
Gronefeld
JR, monitoring
et al. Long-term
of recurrent
atrial
fibrillation
documented
by G,
an Ehrlich
implantable
device: risk
implications
for optimal
fibrillation
as Jdocumented
by an
implantable monitoring device: implications for optimal
patient
care.
Am Coll Cardiol
2004;43:4752.
patient care. J Am Coll Cardiol 2004;43:4752.
(72) Page RL, Wilkinson WE, Clair WK, et al. Asymptomatic arrhythmias in patients with
(72) Page RL,paroxysmal
Wilkinson WE,
WK, etand
al. Asymptomatic
arrhythmias in patients
with
symptomatic
atrialClair
fibrillation
paroxysmal supraventricular
tachycardia.
symptomatic
paroxysmal7.
atrial fibrillation and paroxysmal supraventricular tachycardia.
Circulation 1994;89:224
Circulation 1994;89:224 7.
(73) Page RL, Tilsch TW, Connolly SJ, et al. Asymptomatic or silent atrial fibrillation:
(73) Page RL,
TW, Connolly
et al.
Asymptomatic
or silent
atrial Circulation
fibrillation:
frequency
in Tilsch
untreated
patients SJ,
and
patients
receiving
azimilide.
frequency in untreated patients and patients receiving azimilide. Circulation
2003;107:11415.
2003;107:11415.
(74) Kumagai K, Nakashima H, Urata H, et al. Effects of angiotensin II type 1 receptor
(74) Kumagai
Nakashima
H, Urata H,
et al. Effects
of angiotensin
typeColl
1 receptor
antagonist
on K,
electrical
and structural
remodeling
in atrial
fibrillation. JII Am
Cardiol
antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol
2003;41:2197204.
2003;41:2197204.
(75) Herweg B, Dalal P, Nagy B, et al. Power spectral analysis of heart period variability
(75)
Herweg B,
Dalal
P, Nagy
B, etinitiation
al. Power
spectral analysis
heart period
of
preceding
sinus
rhythm
before
of paroxysmal
atrial of
fibrillation.
Am variability
J Cardiol
of preceding 74.
sinus rhythm before initiation of paroxysmal atrial fibrillation. Am J Cardiol
1998;82:869
1998;82:869 74.
90
(76) Kerr CR, Boone J, Connolly SJ, et al. The Canadian Registry of Atrial Fibrillation: a
noninterventional follow-up of patients after the first diagnosis of atrial fibrillation. Am J
Cardiol 1998;82:82N5N.
(77) The Stroke Prevention in Atrial Fibrillation Investigators. Predictors of
thromboembolism in atrial fibrillation: II. Echocardiographic features of patients at risk.
Ann Intern Med 1992;116:6 12.
(78) Heart rate variability: standards of measurement, physiological interpretation and
clinical use. Task Force of the European Society of Cardiology and the North American
Society of Pacing and Electrophysiology. Circulation 1996;93:1043 65.
(79) Frustaci A, Chimenti C, Bellocci F, et al. Histological substrate of atrial biopsies in
patients with lone atrial fibrillation. Circulation 1997;96:11804.
(80) Tsai LM, Lin LJ, Teng JK, et al. Prevalence and clinical significance of left atrial
thrombus in nonrheumatic atrial fibrillation. Int J Cardiol 1997;58:1639.
(81) Holmes DR, Reddy VY, Turi ZG, Doshi SK, Sievert H, Buchbinder M, Mullin CM,
Sick P. Percutaneous closure of the left atrial appendage versus warfarin therapy for
prevention of stroke in patients with atrial fibrillation: a randomised noninferiority trial.
Lancet 2009;374:534542.
(82) Pisters R, Lane DA, Nieuwlaat R, de Vos CB, Crijns HJ, Lip GY. A novel
userfriendly score (HAS-BLED) to assess one-year risk of major bleeding in atrial
fibrillation patients: The Euro Heart Survey. Chest 2010; March 18 [Epub ahead of print].
(83) Fang MC, Go AS, Hylek EM, Chang Y, Henault LE, Jensvold NG, Singer DE. Age
and the risk of warfarin-associated hemorrhage: the anticoagulation and risk factors in
atrial fibrillation study. J Am Geriatr Soc 2006;54:12311236.
(84) Van Gelder IC, Groenveld HF, Crijns HJ, Tuininga YS, Tijssen JG, Alings AM,
Hillege HL, Bergsma-Kadijk JA, Cornel JH, Kamp O, Tukkie R, Bosker HA, Van
Veldhuisen DJ, Van den Berg MP. Lenient versus strict rate control in patients with atrial
fibrillation. N Engl J Med 2010;362:13631373.
(85) Hohnloser SH, Crijns HJ, van Eickels M, Gaudin C, Page RL, Torp-Pedersen
C,Connolly SJ. Effect of dronedarone on cardiovascular events in atrial fibrillation. N
Engl J Med 2009;360:668678.
(86) Singh BN, Connolly SJ, Crijns HJ, Roy D, Kowey PR, Capucci A, Radzik D, Aliot
EM, Hohnloser SH. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or
flutter. N Engl J Med 2007;357:987999.
(87) Davy JM, Herold M, Hoglund C, Timmermans A, Alings A, Radzik D, Van Kempen
L. Dronedarone for the control of ventricular rate in permanent atrial fibrillation: the
Efficacy and safety of dRonedArone for the cOntrol of ventricular rate during atrial
fibrillation (ERATO) study. Am Heart J 2008;156:527.e1527.e9.
(88) Murgatroyd FD, Gibson SM, Baiyan X, ONunain S, Poloniecki JD, Ward DE, Malik
M, Camm AJ. Double-blind placebo-controlled trial of digoxin in symptomatic
paroxysmal atrial fibrillation. Circulation 1999;99:27652770.
(89) Farshi R, Kistner D, Sarma JS, et al. Ventricular rate control in chronic atrial
fibrillation during daily activity and programmed exercise: a crossover open-label study
of five drug regimens. J Am Coll Cardiol 1999;33:304 10.
(90) Ozcan C, Jahangir A, Friedman PA, Patel PJ, Munger TM, Rea RF, Lloyd MA,
Packer DL, Hodge DO, Gersh BJ, Hammill SC, Shen WK. Long-term survival after
ablation of the atrioventricular node and implantation of a permanent pacemaker in
patients with atrial fibrillation. N Engl J Med 2001;344:10431051.
91
(100) Weerasooriya R, Davis M, Powell A, Szili-Torok T, Shah C, Whalley D,

Kanagaratnam L, Heddle W, Leitch J, Perks A, Ferguson L, Bulsara M. The Australian
intervention randomized control of rate in atrial fibrillation trial (AIRCRAFT). J Am Coll
Cardiol 2003;41:16971702.
(101) Gasparini M, Auricchio A, Metra M, Regoli F, Fantoni C, Lamp B, Curnis A, Vogt J,
Klersy C. Long-term survival in patients undergoing cardiac resynchronization therapy:
the importance of performing atrio-ventricular junction ablation in patients with
permanent atrial fibrillation. Eur Heart J 2008;29:16441652.
(102) Upadhyay GA, Choudhry NK, Auricchio A, Ruskin J, Singh JP. Cardiac
resynchronization in patients with atrial fibrillation: a meta-analysis of prospective cohort
studies. J Am Coll Cardiol 2008;52:12391246.
(103) Auricchio A, Metra M, Gasparini M, Lamp B, Klersy C, Curnis A, Fantoni C,
Gronda E, Vogt J. Long-term survival of patients with heart failure and ventricular
conduction delay treated with cardiac resynchronization therapy. Am J Cardiol
2007;99:232238.
(104) Dong K, Shen WK, Powell BD, Dong YX, Rea RF, Friedman PA, Hodge DO,
Wiste HJ, Webster T, Hayes DL, Cha YM. Atrioventricular nodal ablation predicts
survival benefit in patients with atrial fibrillation receiving cardiac resynchronization
therapy. Heart Rhythm 2010; Feb 17 [Epub ahead of print].
(105) Lafuente-Lafuente C, Mouly S, Longas-Tejero MA, Bergmann JF. Antiarrhythmics
for maintaining sinus rhythm after cardioversion of atrial fibrillation. Cochrane Database
Syst Rev 2007;4:CD005049.
(106) McNamara RL, Bass EB, Miller MR, Segal JB, Goodman SN, Kim NL, Robinson
KA, Powe NR. Management of new onset atrial fibrillation (evidence report/Technology
assessment). In: Agency for Heathcare Research and Quality. 2001, Publication No.
AHRQ 01-E026.
(107) Karlson BW, Torstensson I, Abjorn C, Jansson SO, Peterson LE. Disopyramide in
the maintenance of sinus rhythm after electroconversion of atrial fibrillation. A placebocontrolled one-year follow-up study. Eur Heart J 1988;9:284290.
(108) Crijns HJ, Gosselink AT, Lie KI. Propafenone versus disopyramide for
maintenance of sinus rhythm after electrical cardioversion of chronic atrial fibrillation: a
randomized, double-blind study. PRODIS Study Group. Cardiovasc Drugs Ther
1996;10:145152.
(109) Connolly SJ. Evidence-based analysis of amiodarone efficacy and safety.
Circulation 1999;100:20252034.
(110) Piccini JP, Hasselblad V, Peterson ED,Washam JB, Califf RM, Kong DF.
Comparative efficacy of dronedarone and amiodarone for the maintenance of sinus
rhythm in patients with atrial fibrillation. J Am Coll Cardiol 2009;54:10891095.
(111) Freemantle N, Mitchell S, Orme M, Eckert L, Reynolds MR. Morbidity and
mortality associated with anti-arrhythmic drugs in atrial fibrillation: a systematic review
and mixed treatment meta-analysis (abstract). Circulation 2009;120:S691S692.
(112) Kober L, Torp-Pedersen C, McMurray JJ, Gotzsche O, Levy S, Crijns H, Amlie J,
Carlsen J. Increased mortality after dronedarone therapy for severe heart failure. N Engl
J Med 2008;358:26782687.
(113) Roy D, Talajic M, Dorian P, Connolly S, Eisenberg MJ, Green M, Kus T, Lambert
J, Dubuc M, Gagne P, Nattel S, Thibault B. Amiodarone to prevent recurrence of atrial
fibrillation. Canadian Trial of Atrial Fibrillation Investigators. N Engl J Med
2000;342:913920.
92
(114) Van Gelder IC, Crijns HJ, Van Gilst WH, Van Wijk LM, Hamer HP, Lie KI. Efficacy
and safety of flecainide acetate in the maintenance of sinus rhythm after electrical
cardioversion of chronic atrial fibrillation or atrial flutter. Am J Cardiol 1989;64:1317
1321.
(115) Singh SN, Fletcher RD, Fisher SG, Singh BN, Lewis HD, Deedwania PC, Massie
BM, Colling C, Lazzeri D. Amiodarone in patients with congestive heart failure and
asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in
Congestive Heart Failure. N Engl J Med 1995;333:7782.
(116) Singh D, Cingolani E, Diamon GA, Kaul S. Dronedarone for atrial fibrillation: have
we expanded the antiarrhythmic armamentarium. J Am Coll Cardiol 2010;55:15691576.
(117) Calkins H, Reynolds MR, Spector P, Sondhi M, Xu Y, Martin A, Williams CJ,
Sledge I. Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency
ablation: two systematic literature reviews and meta-analyses. Circ Arrhythm
Electrophysiol 2009;2:349361.
(118) Wazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, SalibaW, Bash D,
Schweikert R, Brachmann J, Gunther J, Gutleben K, Pisano E, Potenza D, Fanelli R,
Raviele A, Themistoclakis S, Rossillo A, Bonso A, Natale A. Radiofrequency ablation vs
antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a
randomized trial. JAMA 2005;293:26342640.
(119) Gaita F, Riccardi R, Caponi D, Shah D, Garberoglio L, Vivalda L, Dulio A,
Chiecchio A, Manasse E, Gallotti R. Linear cryoablation of the left atrium versus
pulmonary vein cryoisolation in patients with permanent atrial fibrillation and valvular
heart disease: correlation of electroanatomic mapping and longterm clinical results.
Circulation 2005;111:136142.
(120) Cox JL, Boineau JP, Schuessler RB, Ferguson TB Jr, Cain ME, Lindsay BD, Corr
PB, Kater KM, Lappas DG. Successful surgical treatment of atrial fibrillation. Review
and clinical update. JAMA 1991;266:19761980.
(121) Noheria A, Kumar A, Wylie JV Jr, Josephson ME. Catheter ablation vs
antiarrhythmic drug therapy for atrial fibrillation: a systematic review. Arch Intern Med
2008;168:581586.
(122) Jais P, Cauchemez B, Macle L, Daoud E, Khairy P, Subbiah R, Hocini M,
Extramiana F, Sacher F, Bordachar P, Klein G, Weerasooriya R, Clementy J,
Haissaguerre M. Catheter ablation versus antiarrhythmic drugs for atrial fibrillation:the
A4 study. Circulation 2008;118:24982505.
(123) Pappone C, Augello G, Sala S, Gugliotta F, Vicedomini G, Gulletta S, Paglino G,
Mazzone P, Sora N, Greiss I, Santagostino A, LiVolsi L, Pappone N, Radinovic A,
Manguso F, Santinelli V. A randomized trial of circumferential pulmonary vein ablation
versus antiarrhythmic drug therapy in paroxysmal atrial fibrillation:the APAF Study. J
Am Coll Cardiol 2006;48:23402347.
(124) Piccini JP, Lopes RD, Kong MH, Hasselblad V, Jackson K, Al-Khatib SM.
Pulmonary vein isolation for the maintenance of sinus rhythm in patients with atrial
fibrillation: a meta-analysis of randomized, controlled trials. Circ Arrhythm Electrophysiol
2009;2:626633.
(125) Nair GM, Nery PB, Diwakaramenon S, Healey JS, Connolly SJ, Morillo CA. A
systematic review of randomized trials comparing radiofrequency ablation with
antiarrhythmic medications in patients with atrial fibrillation. J Cardiovasc Electrophysiol
2009;20:138144.
93
(126) Blanc JJ, Almendral J, Brignole M, Fatemi M, Gjesdal K, Gonzalez-Torrecilla E,

Kulakowski P, Lip GY, Shah D, Wolpert C. Consensus document on antithrombotic
therapy in the setting of electrophysiological procedures. Europace 2008;10:513527.
(127) Ngaage DL, Schaff HV, Mullany CJ, Barnes S, Dearani JA, Daly RC, Orszulak TA,
Sundt TM 3rd. Influence of preoperative atrial fibrillation on late results of mitral repair:
is concomitant ablation justified? Ann Thorac Surg 2007;84:434442; discussion 442
443.
(128) Gaita F, Riccardi R, Gallotti R. Surgical approaches to atrial fibrillation. Card
Electrophysiol Rev 2002;6:401405.
(129) Atwood JE, Myers J, Sandhu S, et al. Optimal sampling interval to estimate heart
rate at rest and during exercise in atrial fibrillation. Am J Cardiol 1989;63:45 8.
(130) Olshansky B, Rosenfeld LE, Warner AL, et al. The Atrial Fibrillation Follow-up
Investigation of Rhythm Management (AFFIRM) study:approaches to control rate in
atrial fibrillation. J Am Coll Cardiol 2004;43:1201 8.
(131) Lemery R, Brugada P, Cheriex E, et al. Reversibility of tachycardia-induced left
ventricular dysfunction after closed-chest catheter ablation of the atrioventricular
junction for intractable atrial fibrillation. Am J Cardiol 1987;60:14068.
(132) Roberts SA, Diaz C, Nolan PE, et al. Effectiveness and costs of digoxin treatment
for atrial fibrillation and flutter. Am J Cardiol 1993;72:56773.
(133) Kay GN, Ellenbogen KA, Giudici M, et al. The Ablate and Pace Trial:a prospective
study of catheter ablation of the AV conduction system and permanent pacemaker
implantation for treatment of atrial fibrillation. APT Investigators. J Interv Card
Electrophysiol 1998;2:12135.
(134) Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA/ESC guidelines for the
management of patients with atrial fi brillation. A report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines and the
European Society of Cardiology Committee for Practice Guidelines and Policy
Conferences (Committee to Develop Guidelines for the Management of Patients with
Atrial Fibrillation). J Am Coll Cardiol 2001;38(4):1266ilxx.
(135) Savelieva I, Camm AJ. Is there any hope for angiotensin-converting enzyme
inhibitors in atrial fibrillation? Am Heart J 2007;154:403406.
(136) Schneider MP, Hua TA, Bohm M, Wachtell K, Kjeldsen SE, Schmieder RE.
Prevention of atrial fibrillation by reninangiotensin system inhibition a meta-analysis. J
Am Coll Cardiol 2010;55:22992307.
(137) Healey JS, Baranchuk A, Crystal E, Morillo CA, Garfinkle M, Yusuf S, Connolly SJ.
Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and
angiotensin receptor blockers: a meta-analysis. J Am Coll Cardiol 2005;45:18321839.
(138) Jibrini MB, Molnar J, Arora RR. Prevention of atrial fibrillation by way of
abrogation of the reninangiotensin system: a systematic review and meta-analysis. Am
J Ther 2008;15:3643.
(139) Anand K, Mooss AN, Hee TT, Mohiuddin SM. Meta-analysis: inhibition of renin
angiotensin system prevents new-onset atrial fibrillation. Am Heart J 2006;152:217222.
(140) Ducharme A, Swedberg K, Pfeffer MA, Cohen-Solal A, Granger CB, Maggioni AP,
Michelson EL, McMurray JJ, Olsson L, Rouleau JL, Young JB, Yusuf S. Prevention of
atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the
Candesartan in Heart failure: assessment of
Reduction in Mortality and morbidity (CHARM) program. Am Heart J 2006; 151:985991.
94
(141) Wachtell K, Lehto M, Gerdts E, Olsen MH, Hornestam B, Dahlof B, Ibsen H, Julius
S, Kjeldsen SE, Lindholm LH, Nieminen MS, Devereux RB. Angiotensin II receptor
blockade reduces new-onset atrial fibrillation and subsequent stroke compared to
atenolol: the Losartan Intervention For End Point Reduction in Hypertension (LIFE)
study. J Am Coll Cardiol 2005;45:712719.
(142) Schmieder RE, Kjeldsen SE, Julius S, McInnes GT, Zanchetti A, Hua TA.
Reduced incidence of new-onset atrial fibrillation with angiotensin II receptor
blockade:the VALUE trial. J Hypertens 2008;26:403411.
(143) Madrid AH, Bueno MG, Rebollo JM, Marin I, Pena G, Bernal E, Rodriguez A,
Cano L, Cano JM, Cabeza P, Moro C. Use of irbesartan to maintain sinus rhythm in
patients with long-lasting persistent atrial fibrillation: a prospective and randomized
study. Circulation 2002;106:331336.
(144) Ueng KC, Tsai TP, Yu WC, Tsai CF, Lin MC, Chan KC, Chen CY, Wu DJ, Lin CS,
Chen SA. Use of enalapril to facilitate sinus rhythm maintenance after external
cardioversion of long-standing persistent atrial fibrillation. Results of a prospective and
controlled study. Eur Heart J 2003;24:20902098.
(145) Tveit A, Seljeflot I, Grundvold I, Abdelnoor M, Smith P, Arnesen H. Effect of
candesartan and various inflammatory markers on maintenance of sinus rhythm after
electrical cardioversion for atrial fibrillation. Am J Cardiol 2007;99:15441548.
(146) Yin Y, Dalal D, Liu Z, Wu J, Liu D, Lan X, Dai Y, Su L, Ling Z, She Q, Luo K, Woo
K, Dong J. Prospective randomized study comparing amiodarone vs. amiodarone plus
losartan vs. amiodarone plus perindopril for the prevention of atrial fibrillation recurrence
in patients with lone paroxysmal atrial fibrillation. Eur Heart J 2006;27:18411846.
(147) Belluzzi F, Sernesi L, Preti P, Salinaro F, Fonte ML, Perlini S. Prevention of
recurrent lone atrial fibrillation by the angiotensin-II converting enzyme inhibitor ramipril
in normotensive patients. J Am Coll Cardiol 2009;53:2429.
(148) Liakopoulos OJ, Choi YH, Kuhn EW, Wittwer T, Borys M, Madershahian N,
Wassmer G, Wahlers T. Statins for prevention of atrial fibrillation after cardiac surgery: a
systematic literature review. J Thorac Cardiovasc Surg 2009;138:678686 e1.
(149) Savelieva I, Kourliouros A, Camm J. Primary and secondary prevention of atrial
fibrillation with statins and polyunsaturated fatty acids: review of evidence and clinical
relevance. Naunyn Schmiedebergs Arch Pharmacol 2010;381:113.
(150) Patti G, Chello M, Candura D, Pasceri V, DAmbrosio A, Covino E, Di Sciascio G.
Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in
patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for
Reduction of MYocardial Dysrhythmia After cardiac surgery) study. Circulation
2006;114:14551461.
(151) Fauchier L, Pierre B, de Labriolle A, Grimard C, Zannad N, Babuty D.
Antiarrhythmic effect of statin therapy and atrial fibrillation: a meta-analysis of
randomized controlled trials. J Am Coll Cardiol 2008;51:828835.
(152) Liu T, Li L, Korantzopoulos P, Liu E, Li G. Statin use and development of atrial
fibrillation: a systematic review and meta-analysis of randomized clinical trials and
observational studies. Int J Cardiol 2008;126:160170.
(153) Crystal E, Garfinkle MS, Connolly SS, Ginger TT, Sleik K, Yusuf SS. Interventions
for preventing post-operative atrial fibrillation in patients undergoing heart surgery.
Cochrane Database Syst Rev 2004;4:CD003611.
(154) Burgess DC, Kilborn MJ, Keech AC. Interventions for prevention of postoperative
atrial fibrillation and its complications after cardiac surgery: a meta-analysis. Eur Heart J
2006;27:28462857.
95
(155) Mathew JP, Fontes ML, Tudor IC, Ramsay J, Duke P, Mazer CD, Barash PG, Hsu
PH, Mangano DT. A multicenter risk index for atrial fibrillation after cardiac surgery.
JAMA 2004;291:17201729.
(156) Patel AA, White CM, Gillespie EL, Kluger J, Coleman CI. Safety of amiodarone in
the prevention of postoperative atrial fibrillation: a meta-analysis. Am J Health Syst
Pharm 2006;63:829837.
(157) Ho KM, Tan JA. Benefits and risks of corticosteroid prophylaxis in adult cardiac
surgery: a doseresponse meta-analysis. Circulation 2009;119:18531866.
(158) Dunning J, Treasure T, Versteegh M, Nashef SA. Guidelines on the prevention
and management of de novo atrial fibrillation after cardiac and thoracic surgery. Eur J
Cardiothorac Surg 2006;30:852872.
(159) Daoud EG. Management of atrial fibrillation in the post-cardiac surgery setting.
Cardiol Clin 2004;22:159166.
(160) Bagshaw SM, Galbraith PD, Mitchell LB, Sauve R, Exner DV, Ghali WA.
Prophylactic amiodarone for prevention of atrial fibrillation after cardiac surgery: a metaanalysis. Ann Thorac Surg 2006;82:19271937.
(161) Wells JL Jr, MacLean WA, James TN, et al. Characterization of atrial flutter.
Studies in man after open heart surgery using fixed atrial electrodes. Circulation
1979;60:66573.
(162) Schmitt J, Duray G, Gersh BJ, Hohnloser SH. Atrial fibrillation in acute myocardial
infarction: a systematic review of the incidence, clinical features and prognostic
implications. Eur Heart J 2009;30:10381045.
(163) Echt DS, Liebson PR, Mitchell LB, Peters RW, Obias-Manno D, Barker AH,
Arensberg D, Baker A, Friedman L, Greene HL, Huther ML, Richardson DW,
Investigators and the CAST investigators. Mortality and morbidity in patients receiving
encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression
Trial. N Engl J Med 1991;324:781788.
(164) Blomstrom-Lundqvist C, Scheinman MM, Aliot EM, Alpert JS, Calkins H, Camm
AJ, Campbell WB, Haines DE, Kuck KH, Lerman BB, Miller DD, Shaeffer CW,
Stevenson WG, Tomaselli GF, Antman EM, Smith SC Jr, Faxon DP, Fuster V, Gibbons
RJ, Gregoratos G, Hiratzka LF, Hunt SA, Jacobs AK, Russell RO Jr, Priori SG, Blanc JJ,
Budaj A, Burgos EF, Cowie M,Deckers JW, Garcia MA, Klein WW, Lekakis J, Lindahl B,
Mazzotta G, Morais JC, Oto A, Smiseth O, Trappe HJ. ACC/AHA/ESC guidelines for the
management of patients with supraventricular arrhythmiasexecutive summary. a
report of the American College of Cardiology/American Heart Association task force on
practice guidelines and the European Society of Cardiology committee for practice
guidelines (writing committee to develop guidelines for the management of patients with
supraventricular arrhythmias) developed in collaboration with NASPE-Heart Rhythm
Society. J Am Coll Cardiol 2003;42:149314531.
(165) Wellens HJ. Should catheter ablation be performed in asymptomatic patients with
WolffParkinsonWhite syndrome? When to perform catheter ablation in asymptomatic
patients with a WolffParkinsonWhite electrocardiogram. Circulation 2005;112:2201
2297; discussion 2216.
(166) Pappone C, Santinelli V, Manguso F, Augello G, Santinelli O, Vicedomini G,
Gulletta S, Mazzone P, Tortoriello V, Pappone A, Dicandia C, Rosanio S. A randomized
study of prophylactic catheter ablation in asymptomatic patients with the Wolff
ParkinsonWhite syndrome. N Engl J Med 2003;349:18031811.
(167) Bryg RJ, Gordon PR, Kudesia VS, et al. Effect of pregnancy on pressure gradient
in mitral stenosis. Am J Cardiol 1989;63:3846.
96
(168) Whittemore R, Hobbins JC, Engle MA. Pregnancy and its outcome in women with
and without surgical treatment of congenital heart disease. Am J Cardiol 1982;50:641
51.
(169) Forfar JC, Miller HC, Toft AD. Occult thyrotoxicosis: a correctable cause of
idiopathic atrial fibrillation. Am J Cardiol 1979;44:9 12.
(170) Page RL. Treatment of arrhythmias during pregnancy. Am Heart J 1995;130:871
6.
(171) Cox JL, Gardner MJ. Cardiovascular drugs in pregnancy and lactation. In:
Gleicher N, Gall SA, Sibai BM, et al., editors. Principles and Practice of Medical
Therapy in Pregnancy. Stamford, CT: Appleton&Lange, 1998:91126.
(172) Chow T, Galvin J, McGovern B. Antiarrhythmic drug therapy in pregnancy and
lactation. Am J Cardiol 1998;82:58I 62I.
(173) Wagner X, Jouglard J, Moulin M, et al. Coadministration of flecainide acetate and
sotalol during pregnancy: lack of teratogenic effects, passage across the placenta, and
excretion in human breast milk. Am Heart J 1990;119:700 2.
(174) Vaughan Williams EM. A classification of antiarrhythmic actions reassessed after
a decade of new drugs. J Clin Pharmacol 1984;24:12947.
(175) Lownes HE, Ives TJ. Mexiletine use in pregnancy and lactation. Am J Obstet
Gynecol 1987;157:446 7.
(176) Ovadia M, Brito M, Hoyer GL, et al. Human experience with amiodarone in the
embryonic period. Am J Cardiol 1994;73:316 7.
(177) Magee LA, Downar E, Sermer M, et al. Pregnancy outcome after gestational
exposure to amiodarone in Canada. Am J Obstet Gynecol 1995;172:130711.
(178) Foster CJ, Love HG. Amiodarone in pregnancy. Case report and review of the
literature. Int J Cardiol 1988;20:30716.
(179) Leung CY, Brodsky MA. Cardiac arrhythmias and pregnancy. In: Elkayam U,
Gleicher N, editors. Cardiac Problems in Pregnancy. New York: Wiley-Liss, 1998:155
75.
(180) Bates SM, Greer IA, Pabinger I, Sofaer S, Hirsh J. Venous thromboembolism,
thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest
Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest
2008;133:p844S886S.
(181) Chen MS, McCarthy PM, Lever HM, Smedira NG, Lytle BL. Effectiveness of atrial
fibrillation surgery in patients with hypertrophic cardiomyopathy. Am J Cardiol
2004;93:373375.
(182) Maron BJ, Olivotto I, Bellone P, Conte MR, Cecchi F, Flygenring BP, Casey SA,
Gohman TE, Bongioanni S, Spirito P. Clinical profile of stroke in 900 patients with
hypertrophic cardiomyopathy. J Am Coll Cardiol 2002;39:301307.
(183) Bertini M, Borleffs JW, Delgado V, Ng AA, Piers SR, Shanks M, Antoni LM, Biffi M,
Boriani G, Schalij M, Bax JJ, Van de Veire N. Prediction of atrial fibrillation in patients
with implantable cardioverter-defibrillator and heart failure. Eur J Heart Fail 2010;in
press.
(184) Fauchier L, Grimard C, Pierre B, Nonin E, Gorin L, Rauzy B, Cosnay P, Babuty D,
Charbonnier B. Comparison of beta blocker and digoxin alone and in combination for
97
management of patients with atrial fibrillation and heart failure. Am J Cardiol

2009;103:248254.
(185) Nasr IA, Bouzamondo A, Hulot JS, Dubourg O, Le Heuzey JY, Lechat P.
Prevention of atrial fibrillation onset by beta-blocker treatment in heart failure: a metaanalysis. Eur Heart J 2007;28:457462.
(186) Deedwania PC, Singh BN, Ellenbogen K, Fisher S, Fletcher R, Singh SN.
Spontaneous conversion and maintenance of sinus rhythm by amiodarone in patients
with heart failure and atrial fibrillation: observations from the veterans affairs congestive
heart failure survival trial of antiarrhythmic therapy (CHF-STAT). The Department of
Veterans Affairs CHF-STAT Investigators. Circulation 1998;
98:25742579.
(187) Shelton RJ, Clark AL, Goode K, Rigby AS, Houghton T, Kaye GC, Cleland JG. A
randomised, controlled study of rate versus rhythm control in patients with chronic atrial
fibrillation and heart failure: (CAFE-II Study). Heart 2009;95:924930.
(188) Aizer A, Gaziano JM, Cook NR, Manson JE, Buring JE, Albert CM. Relation of
vigorous exercise to risk of atrial fibrillation. Am J Cardiol 2009;103:15721577.
(189) Mozaffarian D, Furberg CD, Psaty BM, Siscovick D. Physical activity and
incidence of atrial fibrillation in older adults: the cardiovascular health study. Circulation
2008;118:800807.
(190) Mont L, Sambola A, Brugada J, Vacca M, Marrugat J, Elosua R, Pare C, Azqueta
M, Sanz G. Long-lasting sport practice and lone atrial fibrillation. Eur Heart J
2002;23:477482.
(191) Heidbuchel H, Anne W, Willems R, Adriaenssens B, Van de Werf F, Ector H.
Endurance sports is a risk factor for atrial fibrillation after ablation for atrial flutter. Int J
Cardiol 2006;107:6772.
(192) Heidbuchel H, Panhuyzen-Goedkoop N, Corrado D, Hoffmann E, Biffi A, Delise P,
Blomstrom-Lundqvist C, Vanhees L, Ivarhoff P, Dorwarth U, Pelliccia A.
Recommendations for participation in leisure-time physical activity and competitive
sports in patients with arrhythmias and potentially arrhythmogenic conditions Part I:
supraventricular arrhythmias and pacemakers. Eur J Cardiovasc Prev Rehabil
2006;13:475484.
(193) Calvo N, Mont L, Tamborero D, Berruezo A, Viola G, Guasch E, Nadal M, Andreu
D, Vidal B, Sitges M, Brugada J. Efficacy of circumferential pulmonary vein ablation of
atrial fibrillation in endurance athletes. Europace 2010;12:3036.
98
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CPG Management of Atrial Fibrillation

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FOREWORD BY PRESIDENT OF NATIONAL HEART ASSOCIATION

Professor Dr. Sim Kui Hian FNHAM

ABOUT THE GUIDELINE

All statements and recommendations formulated were agreed collectively by

Period of Validity of the Guidelines

Identification of multiple leaders to share the implementation work and ensure

3. Identify an implementation group

Support from medical associations such as the Private Medical Practitioners

4. Carrying out a baseline assessment

5. Developing an action plan

The baseline assessment will have identified which recommendations are

6. Key areas for implementation

GUIDELINE WORKING GROUP

Professor Dato Dr Khalid b Haji Yusoff,

Dato Dr Ravindran Jegasothy

Datuk Dr Razali b Omar

Professor Dr Sim Kui Hian

Dato Dr. Sree Raman

An electrocardiogram (ECG) should be performed in all patients, whether

The stroke risk stratification algorithms, CHADS2 and CHA2DS2VASc,

Antithrombotic therapy should be based upon the absolute risks of stroke/

When choosing either an initial rate-control or rhythm-control strategy, the

When choosing an antiarrhythmic agent for rhythm control strategy, safety

Adapted from the American Heart Association/American College of Cardiology (AHA/

6.1 Risk Stratification For Stroke

Table 1. Classification of AF subtypes

AF that has lasted for

1.3 AF NATURAL TIME COURSE

1.2 TYPES OF ATRIAL FIBRILLATION

AF is a naturally progressive disease except for a small proportion of patients (2AF

1.4 EPIDEMIOLOGY AND PROGNOSIS

Table 2: Clinical events (outcomes) affected by AF

Asymptomatic AF is common even in symptomatic patients, irrespective of

Stroke risk increased; AF is

Hospitalizations are frequent in

to reduced quality of life.

AF is the commonest sustained cardiac arrhythmia. Information on AF in

4. Quality of life and exercise

AF can cause marked distress

Wide variation, from no change

5. Left ventricular function

The mortality rate of patients with AF isto

acute heart failure.

AF is associated with a prothrombotic state, intra-atrial stasis, structural heart

Some of the conditions predisposing to AF may be reversible such as acute

and 20 25% of persistent

2.1.1 CAUSES AND ASSOCIATED CONDITIONS

Are symptoms during the episodes moderate or severethe severity

may be5 expressed

Those with undiagnosed AF can receive treatment sooner if an opportunistic

In patients presenting with any of the following:

In patients presenting with any of the following:

of bedside telemetry, ambulatory Holter recordings and event loop

Table 6 : Clinical Evaluation in Patients With AF

disease. Patients with persistent signs of LV dysfunction and/or signs of

Have the patients symptoms improved on therapy; if not, should other

Are there signs of proarrhythmia or risk of proarrhythmia; if so, should the

Has paroxysmal AF progressed to a persistent/permanent form, in spite of

dose of an antiarrhythmic drug be reduced or a change made to another

Has paroxysmal AF progressed to a persistent/permanent form, in spite of

The diagnosis of AF requires documentation by ECG.2,10

In patients with suspected AF, an attempt to record an ECG should be made